USOO9066945B2

(12) United States Patent (10) Patent No.: US 9.066,945 B2 Turberg et al. (45) Date of Patent: Jun. 30, 2015

(54) ECTOPARASITICIDAL ACTIVE SUBSTANCE 2011, 0021539 A1 1/2011 Schwarz et al. COMBINATIONS 2011/O257231 A1 10/2011 Koyanagi et al. 2011/0306499 A1 12/2011 Bretschneider et al. (75) Inventors: Andreas Turberg, Haan (DE); Ulrich Görgens, Ratingen (DE); Hans-Georg FOREIGN PATENT DOCUMENTS Schwarz, Dorsten (DE); Stefan Werner, EP O382173 A2 8, 1990 Berlin (DE) EP O5395.88 A1 5, 1993 EP 2248422 A1 11 2010 (73) Assignee: Bayer Intellectual Property GmbH, JP 2007091708 4/2007 Monheim (DE) JP 2008110971 5, 2008 JP 2008133273 6, 2008 (*) Notice: Subject to any disclaimer, the term of this WO 2005035486 A1 4/2005 patent is extended or adjusted under 35 WO 2007027842 A1 3, 2007 U.S.C. 154(b) by 32 days. WO 2007043677 A1 4/2007 WO 20070487.33 A1 5/2007 (21) Appl. No.: 13/995,958 WO 2007075459 A2 7/2007 WO 2007O95229 A2 8, 2007 (22) PCT Filed: Dec. 19, 2011 WO 2007125984 A1 11, 2007 WO 2007 149134 A1 12/2007 (86). PCT No.: PCT/EP2011/073280 WO 2008104503 A1 9, 2008 WO 2008128711 A1 10, 2008 S371 (c)(1), WO 2009002809 A2 12/2008 (2), (4) Date: Feb. 17, 2014 WO 2009024541 A2 2, 2009 WO 2009060015 A1 5, 2009 (87) PCT Pub. No.: WO2012/084852 WO 2009097992 A1 8, 2009 PCT Pub. Date: Jun. 28, 2012 WO 2009 112275 A1 9, 2009 WO 2010020522 A1 2, 2010 (65) Prior Publication Data WO 2010043315 A1 4/2010 WO 2010090344 A1 8, 2010 US 2014/0179623 A1 Jun. 26, 2014 OTHER PUBLICATIONS (30) Foreign Application Priority Data Cossio-Bayugar et al., “Cytochrome P-4SO Monooxygenase Gene Dec. 21, 2010 (DE) ...... 10 2010 O63 691 Expression Supports a Multifactorial Origin for Resistance in Ripicephalus microplus.” Research Journal Parasitology, 2008, (51) Int. Cl. 3(2):59-66. A6 IK 45/06 (2006.01) Foil et al., “Factors that influence the prevalence of acaricide resis A 6LX3L/2197 (2006.01) tance and -borne diseases.” Veterinary Parasitology, 2004, AOIN 43/60 (2006.01) 125:163-181. CO7D 40/4 (2006.01) OZoe et al., “The antiparasitic isoxazoline A1443 is a potent blocker CO7D 403/04 (2006.01) of insect ligand-gated chloride channels. Biochemical and Bio CO7D 403/4 (2006.01) physical Research Communications, 2010, 391:744-749. CO7D 405/4 (2006.01) The Pesticide Manual, 14th Edition, British Crop Portection Council, (52) U.S. Cl. 2006, cover sheet, iii, and 1278-1342. CPC ...... A6 IK3I/497 (2013.01): A0IN 43/60 Rosario-Cruz et al., “Genetic basis and impact of tick acaricide (2013.01); C07D401/14 (2013.01); C07D resistance.” Frontiers in Bioscience, Jan. 1, 2009, 14:2657-2665. 403/04 (2013.01); C07D 403/14 (2013.01); C07D405/14 (2013.01); A61K 45/06 (2013.01) * cited by examiner (58) Field of Classification Search USPC ...... 514/28, 255.05, 250:544/405 See application file for complete search history. Primary Examiner — Rei-Tsang Shiao (56) References Cited (57) ABSTRACT U.S. PATENT DOCUMENTS The present application relates to active compound combina 7,872,036 B2 1/2011 Toriyabe et al. 7,897,543 B2 3/2011 Bretschneider et al. tions of pyrazin-2-ylpyrazoles (component A) with at least 8,084,452 B2 12/2011 Jeschke et al. one further ectoparasiticide or synergists (component B), and 8, 106,212 B2 1/2012 Jeschke et al. to products comprising Such active compound combinations. 8,138,213 B2 3/2012 Mita et al. These active compound combinations are suitable for con 8,268,754 B2 9, 2012 Mita et al. 8,367,707 B2 2/2013 Goto et al. trolling animal pests in the field of Veterinary medicine. 8,513,260 B2 * 8/2013 Schwarz et al...... 514,255.05 8,546,577 B2 10/2013 Jeschke et al. 2010/0173948 A1 7, 2010 Lahm et al. 23 Claims, No Drawings US 9,066,945 B2 1. 2 ECTOPARASITICDAL ACTIVE SUBSTANCE alkylsulphanyl. haloalkylsulphanyl, alkylsulphinyl, COMBINATIONS haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, cyano, nitro, alkylcarbonyl, alkoxycarbonyl, alkoxycarbony The present application relates to active compound com lalkyl, carboxyl, carboxamide, dialkylcarboxamide, trialkyl binations of pyrazin-2-ylpyrazoles (component A) with at silyl, amino, alkylamino, dialkylamino, alkylsulphony least one further ectoparasiticide or synergists (component lamino, dialkylsulphonylamino, formyl, —CH=NO H. B), and to products comprising Such active compound com -CH=NO-alkyl, -CH=NO-haloalkyl, -C(CH) binations. These active compound combinations are Suitable —NO H. —C(CH)—NO-alkyl, -C(CH)—NO-ha for controlling animal pests in the field of veterinary medi loalkyl; and phenyl, 2-pyridyl and 3-pyridyl which are C1G. 10 optionally Substituted by one or more halogen atoms, cyano, WO 2007/048733A describes the use of aminopyrazoles nitro, alkyl, alkoxy or haloalkyl, where vicinal alkyl, for controlling phytopathogenic harmful fungi, which in a haloalkyl, alkoxy and/or haloalkoxy groups at the phenyl general manner also includes pyrazin-2-ylpyrazoles. The substituent, 2-pyridyl substituent or 3-pyridyl substituent pyrazin-2-ylpyrazoles carry only hydrogen as Substituent in together with the carbon atoms to which they are attached the 3-position. 15 may form a five- to six-membered cyclic system which con WO 2007/027842A discloses anilinopyrazoles which may tains 0 to oxygen or nitrogenatoms, where two oxygenatoms be substituted in the 1-position of the moiety by are not directly attached to one another, and whose alkyl 2-pyrazines. This international application relates to pharma moiety may optionally be substituted by one or more halogen ceutical applications, in particular to the treatment of diabe atoms and/or further alkyl radicals, tes; an arthropodicidal action is not described. R" represents alkyl which is optionally monosubstituted or The active compounds already known from the publica independently poly Substituted by alkoxy, haloalkoxy, alkyl tions mentioned above have disadvantages in their applica Sulphanyl, haloalkylsulphanyl, alkylsulphinyl, haloalkylsul tion; in particular, they have only unsatisfactory insecticidal phinyl, alkylsulphonyl, haloalkylsulphonyl, alkylcarbonyl, activity, if any. Moreover, for the known classes of active alkoxycarbonyl, hydroxyland/or cycloalkyl; alkenyl which is compounds resistance has already been observed in some 25 optionally monosubstituted or independently polysubstituted applications (Veterinary Parasitology (2004) 125, 163-181; by halogen, alkoxy, haloalkoxy, alkylsulphanyl, haloalkylsul Research Journal Parasitology (2008) 3, 59-66; Frontiers in phanyl, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, Bioscience (2009) 14, 2657-2665). Accordingly, there is a haloalkylsulphonyl, alkylcarbonyl, alkoxycarbonyl and/or need for further and/or parasiticides. cycloalkyl, cycloalkyl which is optionally monosubstituted The pyrazin-2-ylpyrazoles of the formula (I) given below 30 or independently polysubstituted by alkyl, haloalkyl and/or are described in the parallel pending application PCT/ halogen; haloalkyl which is optionally monosubstituted or EP2010/003060 (WO 2010/136145). independently polysubstituted by alkoxy, alkylsulphanyl, Accordingly, it is an object of the present invention to haloalkylsulphanyl, alkylsulphinyl, haloalkylsulphinyl, provide alternative insecticidal and/or parasiticidal products alkylsulphonyl, haloalkylsulphonyl and/or phenyl which is having, compared to the active compounds known from the 35 optionally monosubstituted or independently polysubstituted prior art, improved activity and/or a broader activity spec by halogen, alkyl, haloalkyl and/or alkoxy, phenyl which is trum, in particular in activity-enhancing combination with optionally monosubstituted or independently polysubstituted other ectoparasiticides and/or synergists known in the field of by halogen, alkyl, haloalkyl and/or alkoxy; benzyl which is Veterinary medicine. optionally monosubstituted or independently polysubstituted The active compounds referred to in the present description 40 by halogen, alkyl, haloalkyl and/or alkoxy; cyano, formyl. by their common name are known, for example, from “The alkylcarbonyl, CH-NO H. —CH=NO-alkyl, Pesticide Manual” 14th Ed., British Crop Protection Council -CH=NO-haloalkyl, -C(CH)—NO H. —C(CH)= 2006, and the website http://www.alanwood.net/pesticides. NO-alkyl or —C(CH)—NO-haloalkyl, It has now been found that active compound combinations R represents optionally substituted amino, where amino comprising, as component A, certain pyrazin-2-ylpyrazoles 45 may be monosubstituted or independently disubstituted by and, as component B, a furtherectoparasiticidally active com alkyl, haloalkyl, alkoxyalkyl, alkylsulphanylalkyl, alkylsul pound, have very good ectoparasiticidal activities of Veteri phinylalkyl, alkylsulphonylalkyl, alkylcarbonyl, cycloalkyl, nary relevance. cycloalkylalkyl, alkenyl, where the radicals listed above are Accordingly, the invention relates to products comprising, optionally Substituted by halogen, cyano, alkoxy, alkoxycar as component A, a compound of the general formula (I) 50 bonyl and phenyl, where the phenyl ring is optionally mono or polysubstituted by one or more substituents independently of one another selected from the group consisting of halogen, alkyl, haloalkyl and alkoxy; alkynyl, alkoxycarbonyl, alkeny (I) loxycarbonyl, alkinyloxycarbonyl, alkoxycarbonylalkyl, 55 alkoxycarbonylcarbonyl, heterocyclyl, heteroaryl, heterocy clylalkyl or heteroarylalkyl, where the heterocyclic or het eroaromatic ring may optionally be mono- or poly Substituted by one or more Substituents independently of one another selected from the group consisting of halogen, alkyl, 60 haloalkyl and alkoxy; benzyl or phenylcarbonyl, where the phenyl ring in benzyl and phenylcarbonyl is optionally mono in which or polysubstituted by one or more substituents independently X represents phenyl, 2-pyridyl or 3-pyridyl, each of which of one another selected from the group consisting of halogen, is substituted by one or more substituents selected from the alkyl, haloalkyl and alkoxy, and group consisting of halogen, alkyl, haloalkyl, alkoxy, alkoxy 65 R. R' independently of one another represent hydrogen, alkyl, alkoxyalkoxy, cycloalkyl, alkenyloxy, alkynyloxy, halogen, alkyl, cycloalkyl, haloalkyl, cyano, hydroxyl, benzyloxy, cycloalkylalkoxy, haloalkoxy, haloalkoxyalkyl, formyl, alkylcarbonyl, -CH=NO H. —CH=NO-alkyl, US 9,066,945 B2 3 4 —CH=NO-haloalkyl, -C(CH)—NO H. C(CH)— (b) are more preferred in which the radical X represents NO-alkyl, —C(CH)—NO-haloalkyl, nitro, hydroxyl, SH, phenyl, 2-pyridyl or 3-pyridyl, each of which is substituted by alkoxy, alkylsulphanyl, haloalkylsulphanyl, alkylsulphinyl, one or more Substituents selected from the group consisting haloalkylsulphinyl, alkylsulphonyl or haloalkylsulphonyl, of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulpha R represents halogen, alkyl, haloalkyl, hydroxyl, alkoxy, 5 nyl, haloalkylsulphanyl, alkylsulphinyl, haloalkylsulphinyl, alkoxyalkyl, alkoxyalkoxy, cycloalkyl, alkenyloxy, alkyny alkylsulphonyl, haloalkylsulphonyl, cyano and dialky loxy, benzyloxy, cycloalkylalkoxy, haloalkoxy, haloalkoxy lamino; and phenyl, 2-pyridyl and 3-pyridyl which are alkyl, -SH, alkylsulphanyl, haloalkylsulphanyl, alkylsul optionally Substituted by one or more halogen atoms, cyano, phinyl, haloalkylsulphinyl, alkylsulphonyl, nitro, alkyl, alkoxy or haloalkyl, where vicinal alkyl, haloalkylsulphonyl, cyano, nitro, alkylcarbonyl, alkoxycar- 10 haloalkyl and/or alkoxy groups at the phenyl Substituent, bonyl, alkoxycarbonylalkyl, carboxyl, carboxamide, dialky 2-pyridyl substituent or 3-pyridyl substituent together with lcarboxamide, trialkylsilyl, amino, alkylamino, dialky the carbon atoms to which they are attached may form a five lamino, alkylsulphonylamino, dialkylsulphonylamino, to six-membered cyclic system which contains 1 or 2 oxygen formyl, -CH=NO-H, -CH=NO-alkyl, -CH=NO atoms, where two oxygen atoms are not directly attached to haloalkyl, —C(CH)—NO H. —C(CH)—NO-alkyl, 15 one another, and whose alkyl moiety may optionally be Sub —C(CH)—NO-haloalkyl, heteroaryl, where the heteroaro stituted by one or more halogen atoms and/or further alkyl matic ring may optionally be mono- or poly Substituted by one radicals; or more substituents independently of one another selected (c) are particularly preferred in which the radical X repre from the group consisting of halogen, alkyl, haloalkyl and sents phenyl, 2-pyridyl or 3-pyridyl, each of which is substi alkoxy, 2O tuted by one or more substituents selected from the group or N-oxides or salts thereof, consisting of fluorine, chlorine, bromine, iodine, CF, meth and, as component B, an active compound of the following oxy, ethoxy, trifluoroethoxy, methylsulphanyl, 2.2.2-trif active compound groups I-1 to I-25. (I-1) acetylcholinest luoro-ethylsulphanyl, methylsulphinyl, 2.2.2-trifluoroethyl erase(AChE) inhibitors; (I-2) GABA-gated chloride channel Sulphinyl, methylsulphonyl, 2.2.2-trifluoroethyl-Sulphonyl, antagonists; (I-3) sodium channel modulators/voltage-de- 25 cyano and dimethylamino; and phenyl which is optionally pendent Sodium channel blockers; (I-4) nicotinergic acetyl Substituted by one or more halogen atoms, cyano, nitro, choline receptoragonists; (I-5) allosteric acetylcholine recep methyl, methoxy or CF, where vicinal alkyl oralkoxy groups tor modulators (agonists); (I-6) chloride channel activators; at the phenyl substituent together with the carbon atoms to (I-7) juvenile hormone analogues; (I-8) mite growth inhibi which they are attached may form a five- to six-membered tors; (I-9) Slo-1 and latrophilin receptor agonists; (I-10) oxi- 30 cyclic system which contains 1 or 2 oxygenatoms, where two dative phosphorylation inhibitors, ATP disruptors; (I-11) oxi oxygen atoms are not directly attached to one another, and dative phosphorylation decouplers acting by interrupting the whose alkyl moiety may be substituted by one or more further H proton gradient; (I-12) nicotinergic acetylcholine receptor alkyl radicals; antagonists; (I-13) chitin biosynthesis inhibitors, type 0: (d) are very particularly preferred in which the radical X (I-14) chitin biosynthesis inhibitors, type 1: (I-15) moulting 35 represents phenyl which is substituted at up to three carbon disruptors; (I-16) ecdysone agonists/disruptors; (I-17) octo atoms by Substituents selected from the group consisting of paminergic agonists; (I-18) complex-III electron transport chlorine, alkoxy having up to 4 carbon atoms (for example inhibitors; (I-19) complex-I electron transport inhibitors: methoxy or ethoxy), di(C)-alkylamino (for example dim (I-20) voltage-dependent sodium channel blockers; (I-21) ethylamino) and the group —O—CH2—O—attached via the inhibitors of acetyl-CoA carboxylase; (I-22) complex-II elec- 40 oxygenatoms to two vicinal carbon atoms of the phenyl ring; tron transport inhibitors; (I-23) receptor effectors: for example, X represents 7-chloro-1,3-benzodioxol-5-yl-: (I-24) further active compounds with unknown mechanism of 3,5-dichloro-4-methoxyphenyl: 3,5-dichloro-4-dimethy action, such as, for example, benzoximate, chinomethionat, laminophenyl. cyflumetofen, pyridalyl. , penigequinolone A. In a second embodiment of the present invention, com (I-25) synergists such as MGK264 and piperonyl butoxide 45 pounds of the general formula (I) (PBO). (a) are preferred in which the radical R' represents alkyl Preferred embodiments with respect to the compounds of which is optionally monosubstituted or independently the general formula (I) are described below: poly Substituted by alkoxy, haloalkoxy, alkylsulphanyl. In a first embodiment of the present invention, compounds haloalkylsulphanyl, alkylsulphinyl, haloalkylsulphinyl, of the general formula (I) 50 alkylsulphonyl, haloalkylsulphonyl, alkylcarbonyl, alkoxy (a) are preferred in which the radical X represents phenyl, carbonyl, hydroxyl and/or cycloalkyl; alkenyl which is 2-pyridyl or 3-pyridyl, each of which is substituted by one or optionally monosubstituted or independently polysubstituted more Substituents selected from the group consisting of halo by halogen, alkoxy, haloalkoxy, alkylsulphanyl, haloalkylsul gen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulphanyl. phanyl, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphanyl, alkylsulphinyl, haloalkylsulphinyl, 55 haloalkylsulphonyl, alkylcarbonyl, alkoxycarbonyl and/or alkylsulphonyl, haloalkylsulphonyl, cyano, nitro, dialky cycloalkyl, cycloalkyl which is optionally monosubstituted lamino; and phenyl, 2-pyridyl and 3-pyridyl which are or independently polysubstituted by alkyl, haloalkyl and/or optionally Substituted by one or more halogen atoms, cyano, halogen; haloalkyl which is optionally monosubstituted or nitro, alkyl, alkoxy or haloalkyl, where vicinal alkyl, independently poly Substituted by alkoxy, alkylsulphanyl. haloalkyl and/or alkoxy groups at the phenyl Substituent, 60 haloalkylsulphanyl, alkylsulphinyl, haloalkylsulphinyl, 2-pyridyl substituent or 3-pyridyl substituent together with alkylsulphonyl, haloalkylsulphonyl and/or phenyl: the carbonatoms to which they are attached may form a five CH=NOH, CH=NOCH, and CN: to six-membered cyclic system which contains 0 to 2 oxygen (b) are more preferred in which the radical R' represents or nitrogen atoms, where two oxygen atoms are not directly alkyl which is optionally monosubstituted or independently attached to one another, and whose alkyl moiety may option- 65 poly Substituted by alkoxy; alkenyl which is optionally mono ally be substituted by one or more halogen atoms and/or substituted or independently polysubstituted by halogen; further alkyl radicals; cycloalkyl which is optionally monosubstituted or indepen US 9,066,945 B2 5 6 dently polysubstituted by alkyl, haloalkyl and/or halogen; lamino, dialkylamino, alkylsulphonylamino, dialkylsulpho haloalkyl which is optionally monosubstituted or indepen nylamino, heteroaryl, where the heteroaromatic ring may dently polysubstituted by alkoxy: CH=NOH, CH=NOCH optionally be mono- or polysubstituted by one or more sub and CN: stituents independently of one another selected from the (c) are particularly preferred in which the radical R' rep group consisting of halogen, alkyl, haloalkyl and alkoxy; resents CH, CHCH, CH(CH), CHCHCH, C(CH), (b) are more preferred in which the radical R represents C(OCH)HCHCH, CH(OCH), CH=CH prop-1-en-2- halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulphanyl. yl, cyclopropyl, CF, CHFCH, CHF, CFC1, CFBr, alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, cyano, CFCF, CFCH, CFCFCF, CFCFH, CH=NOH, dialkylamino or heteroaryl, where the heteroaromatic ring CH=NOCH, and CN: 10 (d) are very particularly preferred in which the radical R' may optionally be mono- or poly Substituted by one or more represents CF. substituents independently of one another selected from the In a third embodiment of the present invention, compounds group consisting of halogen and alkyl, and of the general formula (I) are preferred in which the radical R (c) are particularly preferred in which the radical R rep represents amino and Substituted amino, where the Substi 15 resents chlorine, bromine, methyl, CF, methoxy, ethoxy, tuted amino may be monosubstituted or independently dis propoxy, propan-2-yloxy, dimethylamino, cyano, methylsul ubstituted by alkyl, haloalkyl, cycloalkylalkyl, optionally phanyl, methylsulphinyl, methylsulphonyl, 1 H-pyrazol-1-yl, halogen- or phenyl-Substituted alkenyl, alkynyl, heterocycly 1H-imidazol-1-yl and 4-fluoro-1H-pyrazol-1-yl; lalkyl and/or heteroarylalkyl, where the heteroaromatic ring (d) are very particularly preferred in which the radical R may optionally be mono- or poly Substituted by one or more represents methoxy or in particular ethoxy. substituents independently of one another selected from the In the context of the present invention, the compound of the group consisting of halogen, alkyl, haloalkyl and alkoxy; general formula (I) also comprises compounds which are benzyl, where the phenyl ring in benzyl may optionally be quarternized at a nitrogen atom by a) protonation, b) alkyla mono- or poly Substituted by one or more Substituents inde tion or c) oxidation. pendently of one another selected from the group consisting 25 By addition of a Suitable inorganic or organic acid such as, of halogen, alkyl, haloalkyl and alkoxy; for example, HCl, HBr, HSO or HNO, or else oxalic acidor (a) are more preferred in which the radical R represents Sulphonic acids, onto a basic group Such as, for example, amino and Substituted amino, where the Substituted amino amino or alkylamino, the compounds of the general formula may be monosubstituted or independently disubstituted by (I) may form salts. Suitable Substituents such as, for example, alkyl, optionally halogen- or phenyl-substituted alkenyl, 30 Sulphonic acids or carboxylic acids, which are present in alkynyl, heteroarylalkyl, where the heteroaromatic ring may deprotonated form, may form inner salts with groups which optionally be mono- or polysubstituted by one or more sub for their part can be protonated, such as amino groups. Salts stituents independently of one another selected from the may also be formed by replacing the hydrogen of Suitable group consisting of halogen and/or alkyl; benzyl, where the Substituents, such as, for example, Sulphonic acids or car phenyl ring in benzyl may optionally be mono- or poly Sub 35 boxylic acids, by a pharmaceutically Suitable cation. These stituted by one or more substituents independently of one salts are, for example, metal salts, in particular alkali metal another selected from the group consisting of halogen and salts or alkaline earth metal salts, especially sodium salts and alkoxy; potassium salts, or else ammonium salts, salts with organic (b) are particularly preferred in which the radical R rep amines or quartary ammonium salts having cations of the resents amino, methylamino, dimethylamino, benzylamino, 40 formula NRRR"R"+ in which R to R" each independently dibenzylamino, (4-chlorobenzyl)amino, bis(4-chlorobenzyl) represent an organic radical, in particular alkyl, aryl, aralkyl amino, (4-methoxybenzyl)amino, bis(4-methoxybenzyl) or alkylaryl. amino, (2-methylprop-2-en-1-yl)amino, prop-2-en-1- In the general formula (I) and all other formulae in the ylamino, prop-2-yn-1-ylamino, bis(prop-2-yn-1-yl)amino, present invention, the radicals alkyl, alkoxy, haloalkyl, (pyrazin-2-ylmethyl)amino, (6-methylpyridin-2-ylmethyl) 45 haloalkoxy, alkylamino, alkylsulphinyl and alkylsulphonyl, amino, bis(6-methylpyridin-2-ylmethyl)amino and (pyridin and the corresponding unsaturated and/or Substituted radicals 2-ylmethyl)amino; from among these in turn the radical R may in each case be straight-chain or branched in the hydro particularly preferably represents amino (-NH2). carbon skeleton. Unless specifically indicated, in these radi In a fourth embodiment of the present invention, com cals the lower carbon skeletons having, for example, 1 to 6 pounds of the general formula (I) 50 carbonatoms, in particular 1 to 4 carbon atoms, or in the case (a) are preferred in which the radicals R and R' indepen ofunsaturated groups 2 to 6 carbonatoms, in particular 2 to 4 dently of one another represent hydrogen, halogen, alkyl, carbon atoms, are preferred. Alkyl radicals, including in the cycloalkyl, haloalkyl, cyano and/or hydroxyl; composite meanings such as alkoxy, haloalkyl etc., are, for (b) are more preferred in which the radicals R and R' example, methyl, ethyl; propyl Such as n- or isopropyl; butyl independently of one another represent hydrogen, halogen 55 Such as n-, i-, t- or 2-butyl, pentyl Such as n-pentyl, isopentyl and/or alkyl; and neopentyl; hexyl Such as n-hexyl, isohexyl, 3-methylpen (c) are particularly preferred in which the radicals R and tyl, 2,2-dimethylbutyl and 2,3-dimethylbutyl; and heptyl Rindependently of one another represent hydrogen, chlorine Such as n-heptyl, 1-methylhexyl and 1,4-dimethylpentyl; alk and/or methyl: enyl and alkynyl radicals have the meaning of the possible (d) are very particularly preferred in which the radicals R 60 unsaturated radical which correspond to the alkyl radicals and and R represent hydrogen. contain at least one double or triple bond, preferably one In a fifth embodiment of the present invention, compounds double bond or triple bond. Alkenyl is, for example, vinyl, of the general formula (I) 1-allyl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, (a) are preferred in which the radical R represents halogen, but-2-en-1-yl, but-3-en-1-yl, 1-methylbut-3-en-1-yl and alkyl, haloalkyl, hydroxyl, alkoxy, haloalkoxy, alkylsulpha 65 1-methylbut-2-en-1-yl; alkynyl is, for example, ethynyl, pro nyl, haloalkylsulphanyl, alkylsulphinyl, haloalkylsulphinyl, pargyl/propynyl, but-2-yn-1-yl, but-3-yn-1-yl and 1-methyl alkylsulphonyl, haloalkylsulphonyl, cyano, amino, alky but-3-yn-1-yl. US 9,066,945 B2 7 8 Cycloalkyl groups are, for example, cyclopropyl, cyclobu Substituted radicals, such as a substituted alkyl, alkenyl, tyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. The alkynyl, cycloalkyl, cycloalkenyl, aryl, phenyl, benzyl, het cycloalkyl groups may be in bi- or tricyclic form. erocyclyl and heteroaryl radical, refer, for example, to a Sub If haloalkyl groups and haloalkyl radicals of haloalkoxy, stituted radical derived from an unsubstituted basic structure, haloalkenyl, haloalkynyl etc. are stated, for these radicals the 5 where the Substituents are, for example, one or more, prefer lower carbon skeleton having, for example, 1 to 6 carbon ably 1, 2 or 3, radicals from the group consisting of halogen, atoms or 2 to 6, in particular 1 to 4, carbonatoms or preferably alkoxy, alkylthio, hydroxyl, amino, nitro, carboxyl or a group 2 to 4 carbon atoms, and also the corresponding unsaturated equivalent to the carboxyl group, cyano, isocyanato, azido, and/or Substituted radicals are in each case straight-chain or alkoxycarbonyl, alkylcarbonyl, formyl, carbamoyl, mono branched in the carbon skeleton. Examples are trifluorom 10 ethyl, difluoromethyl, 2.2.2-trifluoroethyl, trifluoroallyl and and dialkylaminocarbonyl. Substituted amino, Such as acy 1-chloroprop-1-yl-3-yl. lamino, mono- and dialkylamino, trialkylsilyl and optionally In these radicals, alkylene groups are the lower carbon Substituted cycloalkyl, optionally substituted aryl, optionally skeletons having, for example, 1 to 10 carbon atoms, in par substituted heterocyclyl, where each of the lastmentioned ticular 1 to 6 carbon atoms or preferably 2 to 4 carbon atoms, 15 cyclic groups may also be attached via heteroatoms or diva and also the corresponding unsaturated and/or Substituted lent functional groups as in the case of the alkyl radicals radicals in the carbon skeleton, which may in each case be mentioned, and alkylsulphinyl, which includes both enanti straight-chain or branched. Examples are methylene, ethyl omers of the alkylsulphonyl group, alkylsulphonyl, alky ene, n- and isopropylene and n-, S-, iso-, t-butylene. lphosphinyl, alkylphosphonyl and, in the case of cyclic radi In these radicals, hydroxyalkyl groups are the lower carbon cals (="cyclic basic structure'), also alkyl, haloalkyl, skeletons having, for example, 1 to 6 carbon atoms, in par alkylthioalkyl, alkoxyalkyl, optionally Substituted mono- and ticular 1 to 4 carbon atoms, and also the corresponding unsat dialkylaminoalkyl and hydroxyalkyl; the term “substituted urated and/or substituted radicals in the carbon skeleton, radicals' such as substituted alkyl etc. includes as substitu which may in each case be straight-chain or branched. ents in addition to the Saturated hydrocarbon-containing radi Examples are 1,2-dihydroxyethyl and 3-hydroxypropyl. 25 cals mentioned corresponding unsaturated aliphatic and aro Halogen is fluorine, chlorine, bromine or iodine, haloalkyl, matic radicals, such as optionally Substituted alkenyl, -alkenyl and -alkynyl mean alkyl, alkenyl and alkynyl, alkynyl, alkenyloxy, alkynyloxy, alkenylthio, alkynylthio. respectively, partially or fully substituted by halogen, prefer alkenyloxycarbonyl, alkynyloxycarbonyl, alkenylcarbonyl, ably by fluorine, chlorine or bromine, in particular by fluorine alkynylcarbonyl, mono- and dialkenylaminocarbonyl, mono and/or chlorine, for example monohaloalkyl, perhaloalkyl, 30 and dialkynylaminocarbonyl, mono- and dialkenylamino, CF, CHF, CHF, CFCF, CHFCHC1, CC1, CHC1, mono- and dialkynylamino, trialkenylsilyl, trialkynylsilyl, CHCHCl; haloalkoxy is, for example, OCF, OCHF, optionally substituted cycloalkenyl, optionally substituted OCHF, CFCFO, OCHCF and OCHCHCl; this applies cycloalkynyl, phenyl, phenoxy etc. In the case of Substituted correspondingly to haloalkenyland otherhalogen-substituted cyclic radicals having aliphatic moieties in the ring, this also radicals. 35 includes cyclic systems having Substituents which are Aryl is a mono-, bi- or polycyclic aromatic system, for attached to the ring via a double bond, for example substituted example phenyl or naphthyl, preferably phenyl. by an alkylidene group Such as methylidene or ethylidene or A heterocyclic radical (heterocyclyl) contains at least one an oxo group, imino group or Substituted imino group. heterocyclic ring (carbocyclic ring in which at least one If two or more radicals form one or more rings, these may carbon atom is replaced by a heteroatom, preferably by a 40 be carbocyclic, heterocyclic, Saturated, partially saturated, heteroatom from the group consisting of N, O, S. P. B. Si, Se) unsaturated, for example also aromatic and optionally Substi which is saturated, unsaturated or heteroaromatic and may be tuted further. The fused rings are preferably 5- or 6-mem unsubstituted or substituted, where the binding site is located bered rings, benzo-fused cycles being particularly preferred. at a ring atom. The substituents mentioned in an exemplary manner (“first If the heterocyclyl radical or the heterocyclic ring is option 45 substituent level’) may, if they comprise hydrocarbon-con ally substituted, it may be fused with other carbocyclic or taining moieties, optionally be further substituted therein heterocyclic rings. Optionally substituted heterocyclyl also (“second substituent level), for example by one of the sub includes polycyclic systems such as, for example, 8-azabicy stituents as defined for the first substituent level. Correspond clo3.2.1]octanyl or 1-azabicyclo[2.2.1]heptyl. Optionally ing further substituent levels are possible. Preferably, the term Substituted heterocyclyl also includes spirocyclic systems 50 “substituted radicals' only includes one or two substituent Such as, for example, 1-Oxa-5-azaspiro2.3 hexyl. levels. Unless defined otherwise, the heterocyclic ring contains Preferred substituents for the substituent levels are, for preferably 3 to 9 ring atoms, in particular 3 to 6 ring atoms and example, amino, hydroxyl, halogen, nitro, cyano, isocyano, one or more, preferably 1 to 4, in particular 1, 2 or 3, heteroa mercapto, isothiocyanato, carboxyl, carbonamide, SFs, ami toms in the heterocyclic ring, preferably from the group con 55 noSulphonyl, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alky sisting of N, O, and S.; however, two oxygen atoms must not nyl, monoalkylamino, dialkylamino, N-alkanoylamino, be directly adjacent. alkoxy, alkenyloxy, alkynyloxy, cycloalkoxy, cycloalkeny In the context of the present invention, the term heteroaryl loxy, alkoxycarbonyl, alkenyloxycarbonyl, alkynyloxycar is to be understood like systems defined above under "hetero bonyl, aryloxycarbonyl, alkanoyl, alkenylcarbonyl, alkynyl cyclyl': however, these systems are heteroaromatic, i.e. rep 60 carbonyl, arylcarbonyl, alkylthio. cycloalkylthio. resent a completely unsaturated aromatic heterocyclic com alkenylthio, cycloalkenylthio, alkynylthio, alkylsulphenyl, pound. alkylsulphinyl, which includes both enantiomers of the alkyl Unless defined otherwise, the definition “substituted by Sulphinyl group, alkylsulphonyl, monoalkyl-aminosulpho one or more radicals' refers independently of one another to nyl, dialkylaminosulphonyl, alkylphosphinyl, alkylphospho one or more identical or different radicals, where two or more 65 nyl, where alkylphosphinyl and alkylphosphonyl include radicals at a cycle as basic structure may form one or more both enantiomers, N-alkylaminocarbonyl, N,N-dialkylami r1ngs nocarbonyl, N-alkanoylaminocarbonyl, N-alkanoyl-N-alky

US 9,066,945 B2 11 12 , , , promacyl and the ester-free and may be may be mentioned here as being particularly preferred for use mentioned here as being particularly preferred for use against against ectoparasites; or ectoparasites; or organochlorine compounds, for example, , for example , , DDT; or . azinphos (-methyl, -ethyl), cadusafos, , chlo (I-4) Nicotinergic acetylcholine receptoragonists, such as, rfenVinphos, chlormephos, (-methyl), couma for example, nicotine or , for example phos, , demeton-S-methyl, , / , , , , imida DDVP. , , dimethylvinphos, clothiz, , , ; chlothiani , EPN, , , famphur, , din, dinotefuran, imidacloprid, nitenpyram, and thiacloprid , , fosthiazate, heptenophos, isofenphos, 10 may be mentioned here as being particularly preferred for use isopropyl O-(methoxyaminothiophosphoryl) salicylate, against ectoparasites. , , mecarbam, , methi (I-5) Allosteric acetylcholine receptor modulators (ago dathion, , , , , oxy nists). Such as, for example, spinosyns, for example spineto demeton-methyl, (-methyl), , , ram and ; spinosad and spinetoram may be men , , , , pirimiphos 15 tioned here as being particularly preferred for use against (-methyl), , propetamphos, prothiofos, pyraclofos, ectoparasites. pyridaphenthion, quinallphos, Sulfotep, , teme (I-6) Chloride channel activators, such as, for example, phos, , , thiometon, triaZophos, tri avermectinS/milbemycins, for example abamectin, doramec clorfon and vamidothion; azamethiphos, , tin, emamectin benzoate, eprinomectin, ivermectin, latidec chlorpyrifos, , cythioate, diazinon (dimpylate), tin, lepimectin, milbemycin oxime, milbemectin, moxidectin dichlorvos (DDVP), dicrotophos, dimethoate, ethion (di and Selamectin; doramectin, eprinomectin, ivermectin, mil ethion), famphur (famophos), fenitrothion, fenthion (MPP), bemycin oxime, moxidectin and Selamectin may be men heptenophos, malathion, naled, phosmet (PMP, phtalofos), tioned here as being particularly preferred for use against phoxim, propetamphos, temephos, tetrachlorvinphos ectoparasites. (CVMP) and triclorfon/ may be mentioned here 25 (I-7) Juvenile hormone analogues, for example as being particularly preferred for use against ectoparasites. (S—), kinoprene, (S-); or ; (I-2) GABA-gated chloride channel antagonists, such as, ; methoprene (S-) and pyriproxy fen may be for example, organochlorines, for example, bromocyclene, mentioned here as being particularly preferred for use against and (alpha-), , , and ectoparasites. ; endosulphan (alpha-) and lindane may be men 30 (I-8) Mite growth inhibitors, for example clofentezine, tioned here as being particularly preferred for use against diflovidazin, hexythiaZOX, etoxazole; etoxazole may be men ectoparasites; or tioned here as being particularly preferred for use against fiproles (phenylpyrazoles), for example acetoprole, ectoparasites. ethiprole, , pyrafluprole and pyriprole, rizazole; (I-9) Slo-1 and latrophilin receptor agonists, such as, for fipronil and pyriprole may be mentioned here as being par 35 example, cyclic depsipeptides, for example, emodepside and ticularly preferred for use against ectoparasites; or its starting material PF1022A (known from EP 382173, com aryllisoxazolines, arylpyrrolines, arylpyrrolidines, for pound I); emodepside may be mentioned here as being par example, A1443 (known from WO2009/2024541, Ex. 11-1; ticularly preferred for use against ectoparasites. but also compounds from WO 2007/075459, WO 2007/ (I-10). Oxidative phosphorylation inhibitors, ATP disrup 125984, WO 2005/085216, WO 2009/002809), and structur 40 tors. Such as, for example, diafenthiuron. ally related arylpyrrolines (known from WO2009/072621, (I-12) Nicotinergic acetylcholine receptor antagonists, WO 2010020522, WO 2009112275, WO 2009097992, WO Such as, for example, benSultap, cartap (hydrochloride), thio 2009072621, JP 2008133273, JP 2007091708), or arylpyrro cylam, and thiosultap (-Sodium). lidines (WO 2010090344, WO 2010043315, WO (I-13) Chitin biosynthesis inhibitors, type 0, such as, for 2008128711, JP 2008110971), A1443 (=Example 11-1 from 45 example, , for example bistrifluron, chlorflua WO 2009/204541), and also Examples 1 to 4 from US 2010/ Zuron, , flucycloxuron, , hexaflu 0173948 may be mentioned here as being particularly pre muron, , novaluron, noviflumuron, teflubenZuron ferred for use against ectoparasites. and triflumuron; diflubenzuron, fluaZuron, lufenuron and tri (I-3) Sodium channel modulators/voltage-dependent flumuron may be mentioned here as being particularly pre Sodium channel blockers, such as, for example, pyrethroids, 50 ferred for use against ectoparasites. for example , allethrin (d-cis-trans, d-trans), (I-14) Chitin biosynthesis inhibitors, type 1, such as, for , , bioallethrin-S-cyclopentenyl, biores example, . methrin, cycloprothrin, (beta-), (I-15) Moulting disruptors, such as, for example, cyro (gamma-, lambda-), (alpha-, beta-, theta-, mazine and dicyclanil; and dicyclanil may be Zeta-), (1R)-trans-isomers, , 55 mentioned here as being particularly preferred for use against dimefluthrin, (EZ)-(1R)-isomers, esfenvaler ectoparasites. ate, etofenproX, fempropathrin, , flucythrinate, flu (I-16) Ecdysone agonists/disruptors, such as, for example, methrin, fluvalinate (tau-), halfenproX, , metof diacylhydrazines, for example chromafenozide, luthrin, , (1R)-trans-isomer. halofenozide, methoxyfenozide and . , profluthrin, (), , 60 (I-17) Octopaminergic agonists, such as, for example, ami RU 15525, silafluofen, , (1R)-iso traZ, cymiazole and demiditraz, , cymiazole and mers, , and ZXI 8901; the type I demiditraz may be mentioned here as being particularly pre pyrethroids allethrin, bioallethrin, permethrin, phenothrin, ferred for use against ectoparasites. resmethrin, tetramethrin and the type II pyrethroids (alphacy (I-18) Complex-III electron transport inhibitors, such as, anopyrethroids) alpha-cypermethrin, cyfluthrin (beta-), cyha 65 for example, ; acequinocyl; fluacrypyrim. lothrin (lambda-), cypermethrin (alpha-, Zeta-), deltamethrin, (I-19) Complex-I electron transport inhibitors, for example fenvalerate, flucythrinate, , fluvalinate (tau-), and from the group of the METI , for example fenaza US 9,066,945 B2 13 14 quin, fenpyroximate, pyrimidifen, pyridaben, , -continued tolfenpyrad; fenpyroximate, pyrimidifen and tolfenpyrad (B) may be mentioned here as being particularly preferred for use CH3 against ectoparasites: N S -CH3 (I-20) Voltage-dependent sodium channel blockers, such MV as, for example and ; indoxacarb 2 O N and metaflumizone may be mentioned here as being particu C N larly preferred for use against ectoparasites. CN (I-21) Inhibitors of acetyl-CoA carboxylase, such as, for 10 example, tetronic acid derivatives, for example spirodiclofen (also known from WO 2007/149134), (6-trifluoromethylpy and spiromesi?en; or tetramic acid derivatives, for example spirotetramat. ridin-3-yl)methyl(methyl)oxido- '-sulphanylidenecyana (I-22) Complex-II electron transport inhibitors, such as, for mide (known from WO 2007/095229), sulfoxaflor (also example, cyenopyrafen. known from WO 2007/149134), 11-(4-chloro-2,6-dimeth (I-23) Ryanodine receptor effectors. Such as, for example, 15 ylphenyl)-12-hydroxy-1,4-dioxa-9-azadispiro4.2.4.2tet diamides, for example , radec-11-en-10-one (known from WO 2006/089633), 3-(4'- (Rynaxypyr), (Cyazypyr) and also 3-bromo fluoro-2,4-dimethylbiphenyl-3-yl)-4-hydroxy-8-oxa-1- N-2-bromo-4-chloro-6-(1-cyclopropylethyl)carbamoyl azaspiro4.5 dec-3-en-2-one (known from WO 2008/ phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxam 067911), 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethyl) ide (known from WO2005/077934) or methyl 2-3,5- sulphinylphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5- dibromo-2-(3-bromo-1-(3-chloropyridin-2-yl)-1H amine (known from WO 2006/043635), (3S,4aR,12R,12aS, pyrazol-5-yl)carbonyl)amino)benzoyl-1,2- 12bS)-3-(cyclopropylcarbonyl)oxy-6,12-dihydroxy-4, dimethylhydrazinecarboxylate (known from WO2007/ 12b-di-methyl-11-oxo-9-(pyridin-3-yl)-1,3,4,4a,5,6,6a, 12. 043677). 25 12a, 12b-decahydro-2H, 11 H-benzof pyrano.4.3-b- (I-24) Further active compounds with unknown mecha chromen-4-yl)methyl cyclopropanecarboxylate (known nism of action, such as, for example, , amidoflu from WO 2006/129714), 2-cyano-3-(difluoro-methoxy)-N- met, benzoximate, bifenazate, chinomethionat, cryolite, ethylbenzenesulphonamide (known from WO 2005/035486), cyflumetofen, , fluensulfone (5-chloro-2-(3,4,4-trif N-1-(2,3-dimethylphenyl)-2-(3,5-dimethylphenyl)ethyl-4, luorobut-3-en-1-yl)sulphonyl-1,3-thiazole), flufenerim, 30 pyridalyl and pyrifluquinazon; and also products based on 5-dihydro-2-thiazolamine (known from WO 2008/104503); Bacillus firmus (I-1582, BioNeem, Votivo) and also the penigequinolone A (known from EP 2248422 (compound I) known active compounds below 4-(6-bromopyrid-3-yl) and WO 2009/060015 (compound No. 11). methyl(2-fluoroethyl)aminofuran-2(5H)-one (known from (I-25) MGK264 (N-octylbicycloheptenecarboxamide), WO 2007/115644), 4-(6-fluoropyrid-3-yl)methyl(2,2-dif 35 luoroethyl)aminofuran-2(5H)-one (known from WO 2007/ piperonyl butoxide (PBO) and verbutin may be mentioned 115644), 4-(2-chloro-1,3-thiazol-5-yl)methyl(2-fluoroet here as Suitable synergists for use with ectoparasiticides; hyl)aminofuran-2(5H)-one (known from WO 2007/ piperonylbutoxide and MGK264 may be mentioned as being 115644), 4-(6-chloropyrid-3-yl)methyl(2-fluoroethyl) particularly preferred. aminofuran-2(5H)-one (known from WO 2007/115644), 40 From groups (I-1) to (I-25) mentioned above, the following 4-(6-chloropyrid-3-yl)methyl(2,2-difluoroethyl) groups are preferred as component B: (I-2), (I-3). (I-4), (I-5), aminofuran-2(5H)-one (known from WO 2007/115644), 4-(6-chloro-5-fluoropyrid-3-yl)methyl(methyl) (I-6), (I-17), (I-25). aminofuran-2(5H)-one (known from WO 2007/115643), According to a further embodiment, the following groups 4-(5,6-dichloropyrid-3-yl)methyl(2-fluoroethyl) 45 are preferred as component B: (I-2), (I-3). (I-4), (I-5), (I-6), aminofuran-2(5H)-one (known from WO 2007/115646), (I-17). 4-(6-chloro-5-fluoropyrid-3-yl)methyl(cyclopropyl) Preferred examples of insecticidally or acaricidally active aminofuran-2(5H)-one (known from WO 2007/115643), compounds or synergists of component B are endosulphan 4-(6-chloropyrid-3-yl)methyl(cyclopropyl)aminofuran (alpha-), lindane; fipronil, pyriprole; A1443 (Example 11-1 2(5H)-one (known from EP-A-0539.588), 4-(6-chloropy 50 rid-3-yl)methyl(methyl)aminofuran-2(5H)-one (known from WO 2009/2024541); allethrin, bioallethrin, permethrin, from EP-A-0539 588), (6-chloropyridin-3-yl)methyl(me phenothrin, resmethrin, tetramethrin: cyfluthrin (beta-), thyl)oxido-N-sulphanylidenecyanamide (known from WO cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-), delta 2007/149134), 1-(6-chloropyridin-3-yl)ethyl(methyl) methrin, fenvalerate, flucythrinate, flumethrin, fluvalinate oxido-'-sulphanylidenecyanamide (known from WO 2007/ 55 (tau-): etofemproX, Silafluofen; chlothianidin, dinotefuran, 149134) and its diastereomers (A) and (B) imidacloprid, nitenpyram, thiacloprid; spinosad, spinetoram; doramectin, eprinomectin, ivermectin, milbemycin oxime, moxidectin, Selamectin; amitraz, cymiazole, demiditraz: pip CH (A) eronyl butoxide, MGK264. 3 60 Preference is given to active compound combinations N s1 CH3 (Nos. 1 to 39) in which one active compound of component A M is combined with the active compounds below of component F. 2 / \ B, in the mixing ratios given in Table A. These active com N CN 65 pound combinations are listed in Table 3 below. The mixing ratios in the table are based on weight ratios. The ratio is to be understood as meaning component A:component B. US 9,066,945 B2 15 16 TABLE 3 Surprisingly, the insecticidal and/or acaricidal activity of the active compound combinations according to the invention Component B very (=mixing preferre particularly particularly is improved compared to the sum of the activities of the No. partner of mixing preferred preferred individual active compounds in components A and B. A wid Grp. B- component A) ratio mixing ratio mixing ratio 5 ened activity spectrum and/or an improved activity are desir able; preferably, an unforeseeable true synergistic effect is -2 1 Ex. 11-1 from 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 present. WO 2009.2024541 The active compound combinations according to the -3 2 allethrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 invention, in combination with favourable toxicity to warm -17 3 amitraz 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 10 blooded animals and being tolerated well by the environment, -3 4 bioallethrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 -4 5 chlothianidin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 are suitable for use in the animal health field, i.e. in the field -3 6 cyfluthrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 of veterinary medicine. Here, the active compound combina (beta-) tions according to the present invention are active against -3 7 cyhalothrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 animal parasites, in particular ectoparasites. Ectoparasites are (lambda-) 15 -17 8 cymiazole 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 typically and preferably arthropods, in particular insects Such -3 9 cypermethrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 as flies (stinging and licking), parasitic fly larvae, lice, hair (alpha-, Zeta-) lice, bird lice, fleas and the like; or acarids, such as , for -3 10 deltamethrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 examples hard ticks or soft ticks, or mites, such as scab mites, -17 11 demiditraz 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 -4 12 dinotefuran 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 harvest mites, bird mites and the like. -6 13 doramectin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 These parasites include from the order of the Anoplurida, -2 14 endosulphan 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 for example Haematopinus spp., Linognathus spp., Pediculus (alpha-) spp., Phtirus spp., Solenopotes spp.; particular examples are: -6 15 eprinomectin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 -3 16 etofenprox 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 Linognathus setosus, Linognathus vituli, Linognathus Ovil -3 17 fenvalerate 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 lus, Linognathus oviformis, Linognathus pedalis, Linog -2 18 fipronil 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 25 nathus Stenopsis, Haematopinus asini macrocephalus, Hae -3 19 flucythrinate 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 matopinus eurysternus, Haematopinus suis, Pediculus -3 20 flumethrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 -3 21 fluvalinate 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 humanus capitis, Pediculus humanus corporis, Phylloera (tau-) vastatrix, Phthirus pubis, Solenopotes capillatus, -4 22 imidacloprid 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 from the order of the Mallophagida and the suborders -6 23 ivermectin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 30 Amblycerina and Ischnocerina, for example Trimenopon -2 24 lindane 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 -2S 2S MGK264 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 spp., Menopon spp., Trinoton spp., Bovicola spp., Werneck -6 26 milbemycin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 iella spp., Lepikentron spp., Damalina spp., Trichodectes Oxime spp., Felicola spp.; particular examples are: Bovicola bovis, -6 27 moxidectin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 Bovicola ovis, Bovicola limbata, Damalina bovis, Tri -4 28 nitenpyram 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 35 -3 29 permethrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 chodectes canis, Felicola subrostratus, Bovicola Caprae, -3 30 phenothrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 Lepikentron Ovis, Werneckiella equi; -2S 31 piperonyl 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 from the order of the Diptera and the suborders Nemato butoxide cerina and Brachycerina, for example Aedes spp., Anopheles -2 32 pyriprole 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 -3 33 resmethrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 spp., Culex spp., Simulium spp., Eusimulium spp., Phleboto -6 34 sellamectin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 40 mus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., -3 35 sillafluofen 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 Odaginia spp., Wilhelmia spp., Hybomitra spp., Atylotus spp., -S 36 spinetoram 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 Tabanus spp., Haematopota spp., Philipomyia spp., Braula -S 37 spinosad 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 -3 38 tetramethrin 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haemato -4 39 thiacloprid 25:1 to 1:12S 25:1 to 1:25 S:1 to 1:5 bia spp., Morelia spp., Fannia spp., Glossina spp., Calli 45 phora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophi The active compounds of group I-17 have no practically lus spp., Hippobosca spp., Lipoptena spp., Mellophagus spp., relevantactivity towards insects. With regard to the control of insects, according to one embodiment of the present inven Rhinoestrus spp., Tipula spp.; particular examples are: Aedes tion, the active compounds of group I-17 are therefore aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles excluded as component B from the embodiments mentioned 50 gambiae, Anopheles maculipennis, Caliphora erythro above including preferred and particularly preferred cephala, Chrysozona pluvialis, Culex quinquefasciatus, embodiments. Culex pipiens, Culex tarsalis, Fannia canicularis, Sar The active compound combinations according to the cophaga carnaria, Stomoxys calcitrans, Tipula paludosa, invention are highly Suitable for controlling animal pests in Lucilia cuprina, Lucilia sericata, Simulium reptans, Phle the field of veterinary medicine. 55 botomus papatasi, Phlebotomus longipalpis, Odaginia If, in the context of this description, the short form of the ornata, Wilhelmia equina, Boophthora erythrocephala, common name of an active compound is used, this comprises Tabanus bromius, Tabanus Spodopterus, Tabanus atratus, in each case all customary derivatives, such as the esters and Tabanus Sudeticus, Hybomitra ciurea, Chrysops caecutiens, salts, and isomers, in particular optical isomers, especially the Chrysops relictus, Haematopota pluvialis, Haematopota commercially available form or forms. If the common name 60 italica, Musca autumnalis, Musca domestica, Haematobia refers to an ester or a salt, this in each case also comprises all irritans irritans, Haematobia irritans exigua, Haematobia other customary derivatives, such as otheresters and salts, the stimulans, Hydrotaea irritans, Hydrotaea albipuncta, Chry free acids and neutral compounds, and isomers, in particular somya chloropyga, Chrysomya bezziana, Oestrus ovis, Hypo optical isomers, especially the commercially available form derma bovis, Hypoderma lineatum, Przhevalskiana silenus, or forms. The given chemical compound names refer to at 65 Dermatobia hominis, Mellophagus Ovinus, Lipoptena least one of the compounds embraced by the common name, capreoli, Lipoptena cervi, Hippobosca variegata, Hippo frequently to a preferred compound. bOsca equina, Gasterophilus intestinalis, Gasterophilus US 9,066,945 B2 17 18 haemorroidalis, Gasterophilus inermis, Gasterophilus nasa By controlling these arthropods, it is intended to reduce lis, Gasterophilus nigricornis, Gasterophilus pecorum, deaths and improve performance (in the case of meat, milk, Braula coeca, wool, hides, eggs, honey and the like) and health of the host from the order of the Siphonapterida, for example Pulex animal, so that more economical and simpler animal keeping spp., Ctenocephalides spp., Tunga spp., Xenopsylla spp., is made possible by the use of the active compounds accord Ceratophyllus spp.; particular examples are: Ctenocepha ing to the invention. lides canis, Ctenocephalides felis, Pulex irritans, Tunga pen For example, it is desirable to prevent or interrupt the etrans, Xenopsylla cheopis, uptake of blood by the parasites from the host (when appli from the order of the Heteropterida, for example Cimex cable). Also, controlling the parasites may help to prevent the spp., Triatoma spp., Rhodnius spp., Panstrongylus spp. 10 transmittance of infectious agents. from the subclass of the Acari (Acarina) and the orders of The term “controlling as used herein with regard to the the Meta- and Mesostigmata, for example Argas spp., Orni animal health field, means that the active compounds are thodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., effective in reducing the incidence of the respective parasite Rhipicephalus (Boophilus) spp., Dermacentor spp., Haemo in an animal infected with Such parasites to innocuous levels. physalis spp., Hyalomma spp., Dermanyssus spp., Rhipi 15 More specifically, "controlling, as used herein, means that cephalus spp. (the original genus of multi-host ticks) Orni the active compound is effective in killing the respective thonyssus spp., Pneumonyssus spp., Raillietia spp., parasite, inhibiting its growth, or inhibiting its proliferation. Pneumonyssus spp., Sternostoma spp., Varroa spp., Acarapis Generally, when used for the treatment of animals, the spp.; particular examples are: Argas persicus, Argas reflexus, active compounds according to the invention can be applied Ornithodorus moubata, Otobius megnini, Rhipicephalus directly. Preferably they are applied as pharmaceutical com (Boophilus) microplus, Rhipicephalus (Boophilus) decolora positions which may contain pharmaceutically acceptable tus, Rhipicephalus (Boophilus) annulatus, Rhipicephalus excipients and/or auxiliaries which are known in the art. (Boophilus) calceratus, Hvalomma anatolicum, Hvalomma In the animal health field and in animal keeping, the active aegypticum, Hvalomma marginatum, Hvalomma transiens, compounds are applied (administered) in the known manner Rhipicephalus evertsi, Ixodes ricinus, Ixodes hexagonus, 25 by enteral administration in the form of, for example, tablets, Ixodes canisuga, Ixodes pilosus, Ixodes rubicundus, Ixodes capsules, drinks, drenches, granules, pastes, boluses, the scapularis, Ixodes holocyclus, Haemaphysalis concinna, feed-through method, Suppositories; by parenteral adminis Haemaphysalis punctata, Haemaphysalis cinnabarina, tration, such as, for example, by injections (intramuscular, Haemaphysalis Otophila, Haemaphysalis leachi, Haema Subcutaneous, intravenous, intraperitoneal and the like), physalis longicorni, Dermacentor marginiatus, Dermacentor 30 implants, by nasal application, by dermal application in the reticulatus, Dermacentor pictus, Dermacentor albipictus, form of for example, bathing or dipping, spraying, pouring Dermacentor andersoni, Dermacentor variabilis, Hvalomma on and spotting-on, washing, dusting, and with the aid of mauritanicum, Rhipicephalus sanguineus, Rhipicephalus active-compound-comprising shaped articles such as collars, bursa, Rhipicephalus appendiculatus, Rhipicephalus capen ear tags, tail tags, limb bands, halters, marking devices and sis, Rhipicephalus turanicus, Rhipicephalus Zambeziensis, 35 the like. The active compounds may be formulated as sham Amblyomma americanum, Amblyomma variegatum, Amblyo poo or as Suitable formulations usable in aerosols or unpres mma maculatum, Amblyomma hebraeum, Amblyomma Surized sprays, for example pump sprays and atomizer cajennense, Dermanyssus gallinae, Ornithonyssus bursa, SprayS. Ornithonyssus Sylviarum, Varroa jacobsoni; When used for livestock, poultry, domestic animals and the from the order of the Actinedida (Prostigmata) and Acari 40 like, the active compounds according to the invention can be dida (Astigmata), for example Acarapis spp., Cheyletiella applied as formulations (for example powders, wettable pow spp., OrnithOcheyletia spp., Myobia spp., Psorergates spp., ders “WP', emulsions, emulsifiable concentrates “EC. Demodex spp., Trombicula spp., Listrophorus spp., Acarus flowables, homogeneous solutions, and Suspension concen spp., Trophagus spp., Caloglyphus spp., Hypodectes spp., trates “SC) which comprise the active compounds in an Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes 45 amount of from 1 to 80% by weight, either directly or after spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., dilution (e.g. 100- to 10 000-fold dilution), or else as a chemi Cytodites spp., Laminosioptes spp.; particular examples are: cal bath. Cheyletiella vasguri, Cheyletiella blakei, Demodex canis, Naturally, the general broad activity spectrum of the mix Demodex bovis, Demodex ovis, Demodex caprae, Demodex tures in the arthropod field also allows control of hygiene equi, Demodex caballi, Demodex suis, Neotrombicula 50 pests, which are listed below: autumnalis, Neotrombicula desaleri, NeOSchongastia xero From the order of the Heteroptera, for example Anasa thermobia, Trombicula akamushi, Otodectes cynotis, tristis, Antestiopsis spp., Blissus spp., Calocoris spp., Notoedres cati, Sarcoptis canis, Sarcoptes bovis, Sarcoptes Campylomma livida, Cavelerius spp., Cimex spp., Collaria ovis, Sarcoptes rupicaprae (S. Caprae), Sarcoptes equi, Sar spp., Creontiades dilutus, Dasynus piperis, Dichelops firca coptes suis, Psoroptes ovis, Psoroptes cuniculi, Psoroptes 55 tus, Diconocoris hewetti, Dysdercus spp., Euschistus spp., equi, Chorioptes bovis, Psoergates ovis, Pneumonyssoidic Eurygaster spp., Heliopeltis spp., Horcias nobilellus, Lepto mange, Pneumony'ssoides caninum, Acarapis woodi. COrisa spp., Leptoglossus phyllopus, Lygus spp., Macropes The active compound combinations according to the excavatus, Miridae, Monallonion atratum, Nezara spp., invention are also suitable for controlling arthropods which Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus attack animals. Animals include agricultural livestock Such 60 spp., Psallus spp., Pseudacy.sta persea, Rhodnius spp., Sahl as, for example, cattle, sheep, goats, horses, pigs, donkeys, bergella singularis, Scaptocoris Castanea, Scotinophora camels, buffaloes, rabbits, chickens, turkeys, ducks, geese, spp., Stephanitis nashi, Tibraca spp., Triatoma spp. cultured fish, honeybees. Moreover, animals include domes From the order of the Homoptera, for example Acyrtho tic animals—also referred to as companion animals—such Sipon spp., Acrogonia spp., Aeneolamia spp., Agonoscena as, for example, dogs, cats, cage birds, aquarium fish and 65 spp., Aleurodes spp., Aleurolobus barodensis, Aleurothrixus what are known as experimental animals such as, for spp., Amrasca spp., Anuraphis cardui, Aonidiella spp., Apha example, hamsters, guinea pigs, rats and mice. nostigma piri, Aphis spp., Arboridia apicalis, Aspidiella spp., US 9,066,945 B2 19 20 Aspidiotus spp., Atanus spp., Aulacorthum Solani, Bemisia rycter spp., Pieris spp., Platynota Stultana, Plusia spp., Plu spp., Brachycaudus helichrysii, Brachycolus spp., Brevico tella xylostella, Prays spp., Prodenia spp., Protoparce spp., ryne brassicae, Calligpona marginata, Carneocephala Pseudaletia spp., Pseudoplusia includens, Pyrausta nubila fiulgida, Ceratovacuna lanigera, Cercopidae, Ceroplastes lis, Rachiplusia nu, Schoenobius spp., Scirpophaga spp., spp., Chaetosiphon fragaefolii, Chionaspis tegalensis, Chlo Scotia segetum, Sesamia spp., Sparganothis spp., Spodoptera rita Onuki, Chromaphis juglandicola, Chrysomphalus ficus, spp., Stathmopoda spp., Stomopteryx subsecivella, Synanthe Cicadulina mbila, Coccomytilus halli, Coccus spp., Crypto don spp., Tecia Solanivora, Thermesia gemmatalis, Tinea pel myzus ribis, Dalbulus spp., Dialeurodes spp., Diaphorina lionella, Tineola bisselliella, Tortrix spp., Trichoplusia spp., spp., Diaspis spp., Drosicha spp., Dysaphis spp., Dysmicoc Tuta absoluta, Virachola spp. cus spp., Empoasca spp., Eriosoma spp., Erythroneura spp., 10 From the order of the Orthoptera, for example Acheta Euscelis bilobatus, Ferrisia spp., Geococcus coffeae, Hiero domesticus, Blatta Orientalis, Blattella germanica, glyphus spp., Homalodisca coagulata, Hyalopterus arundi Dichroplus spp., Gryllotalpa spp., Leucophaea maderae, nis, Icerya spp., Idiocerus spp., Idioscopus spp., Laodelphax Locusta spp., Melanoplus spp., Supella spp., Periplaneta striatellus, Lecanium spp., Lepidosaphes spp., Lipaphis ery americana, Schistocerca gregaria. simi, Macrosiphum spp., Mahanarva spp., Melanaphis sac 15 From the order of the Symphyla, for example Scutigerella chari, Metcalfiella spp., Metopolophium dirhodium, Monellia spp. costalis, Monelliopsis pecanis, Myzus spp., Nasonovia ribis From the order of the Thysanura, for example Lepisma nigri, Nephotettix spp., Nilaparvata lugens, Oncometopia saccharina. spp., Orthezia praelonga, Parabemisia myricae, Paratrioza “Combination' or the use in combination means that the spp., Parlatoria spp., Pemphigus spp., Peregrinus maidis, components A and B are formulated in a joint preparation and Phenacoccus spp., Phloeomyzus passerinii, Phorodon are accordingly applied together. However, the products may humuli, Phylloxera spp., Pinnaspis aspidistrae, Planococcus also comprise separate preparations for each active com spp., Protopulvinaria pyriformis, Pseudaulacaspis pen pound. Accordingly, if more than two active compounds are tagona, Pseudococcus spp., Psylla spp., Pteromalus spp., to be applied, all active compounds may be formulated in a Pyrilla spp., Ouadraspidiotus spp., Quesada gigas, Rastro 25 coccus spp., Rhopalosiphum spp., Saissetia spp., Scaphoides joint preparation or all active compounds may be formulated titanus, Schizaphis graminum, Selenaspidus articulatus, in separate formulations; also feasible are mixed forms where Sogata spp., Sogatella fircifera, Sogatodes spp., Sticto Some of the active compounds are formulated jointly and cephala festina, Tenalaphara malayensis, Tinocallis carvae Some of the active compounds are formulated separately. foliae, Tomaspis spp., Toxoptera spp., Trialeurodes spp., 30 Separate formulations allow the separate or Successive Trioza spp., Tiphlocyba spp., Unaspis spp., Viteus vitifolii, application of the active compounds in question. Zygiina spp. From the order of the Hymenoptera, for example Athalia EXAMPLES spp., Diprion spp., Hoplocampa spp., Lasius spp., Monomo Preparation Example A-15 rium pharaonis, Vespa spp. 35 From the order of the Isopoda, for example Armadillidium Step 1: vulgare, Oniscus asellus, Porcellio scaber. 3,5-Dichloro-4-(dimethylamino)phenyl)acetonitrile From the order of the Isoptera, for example Acromyrmex spp., Atta spp., Cornitermes cumulans, Microtermes Obesi, Odontotermes spp., Reticulitermes spp. 40 From the order of the Lepidoptera, for example Acronicta major, Adoxophyes spp., Aedia leucomelas, Agrotis spp., Ala N1 bama spp., Amyelois transitella, Anarsia spp., Anticarsia spp., Argyroploce spp., Barathra brassicae, Borbo cinnara, C C -SSi 1. Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., 45 -- 2. " -e- Cacoecia spp., Caloptilia theivora, Capua reticulana, Car pocapsa pomonella, Carposina niponensis, Cheinatobia brumata, Chilo spp., Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnephasia spp., Conopomorpha spp., Br Conotrachelus spp., Copitarsia spp., Cydia spp., Dalaca noc 50 N1 tuides, Diaphania spp., Diatraea saccharalis, Earias spp., C C Ecdytolopha aurantium, Elasmopalpus lignosellus, Eldana saccharina, Ephestia kuehniella, Epinotia spp., Epiphyas postvittana, Etiella spp., Eulia spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia spp., Galleria mellonella, 55 Gracillaria spp., Grapholitha spp., Hedylepta spp., Helicov erpa spp., Heliothis spp., Hofinannophila pseudospretella, Homoeosoma spp., Homona spp., Hyponomeuta padella, 2 Kakivoria flavofasciata, Laphygma spp., Laspeyresia molesta, Leucinodes Orbonalis, Leucoptera spp., Lithocolle 60 In a glass tube with screw-on lid, 2 g (7.43 mmol) of tis spp., Lithophane antennata, Lobesia spp., Loxagrotis albi 4-bromo-2,6-dichloro-N,N-dimethylaniline (known from costa, Lymantria spp., Lyonetia spp., Malacosoma neustria, European Journal of Organic Chemistry (2006), (19), 4398 Maruca testulalis, Mamestra brassicae, Mocis spp., 4404) are initially charged with 86 mg (0.14 mmol) of xant Mythinna separata, Nymphula spp., Oiketicus spp., Oria phos and 136 mg (0.14 mmol) of tris(dibenzylideneacetone)- spp., Orthaga spp., Ostrinia spp., Oulema Oryzae, Panolis 65 dipalladium in 10 ml of DMF, 1.01 g (8.92 mmol) of flammea, Parnara spp., Pectinophora spp., Perileucoptera trimethylsilylacetonitrile and 0.46g (4.46 mmol) of zinc fluo spp., Phthorimaea spp., Phyllocnistis citrella, Phyllono ride are then added, and in the closed vessel the reaction is US 9,066,945 B2 21 22 heated at 90° C. for 16 hours. The reaction mixture is cooled, -continued F water and ethyl acetate are added and the mixture is filtered F through silica gel. C The organic phase is separated off, dried over magnesium F Sulphate and concentrated. The crude product is chromato graphed on a silica gel cartridge using a cyclohexane/ethyl l C acetate gradient. This gives 0.9 g (52.8% of theory) of the title 1N -- Š compound as a colourless oil. 'H-NMR: (400 MHz, DMSO-d6), 8 7.42 (s. 2H), 4.01 (s, 10 2H), 2.81 (s, 6H). 1 g (3.07 mmol) of 2-3,5-dichloro-4-(dimethylamino) Step 2: 2-3,5-Dichloro-4-(dimethylamino)phenyl phenyl-4,4,4-trifluoro-3-oxobutanenitrile is initially 4,4,4-trifluoro-3-oxobutanenitrile 15 charged in 1.44 ml of POCl (15.3 mmol), and 0.43 ml (3.07 mmol) of triethylamine are added slowly. The reaction mix ture is then stirred under reflux for 5 hours. After cooling, water is added carefully and the mixture is extracted repeat N1 edly with dichloromethane. The separated organic phases are 2O C C O combined, dried over magnesium Sulphate, filtered and con F centrated. The residue is used without further purification for -- F + Na-H -e- O the next step. F ls 25 Step 4: (A-15) 2 N1 C CI 30

F C 1s1'N-1 35 2. F

1.41 g (35.3 mmol) of sodium hydride are initially charged 40 in absolute THF (50 ml), and 4.05 g (17.6 mmol) of 3,5- dichloro-4-(dimethylamino)phenyl)acetonitrile in 20 ml of absolute THF are added dropwise at 0°C. The mixture is stirred at 0°C. for 20 minutes, and 5.02 g (35.3 mmol) of ethyl trifluoroacetate are then added dropwise at 0°C. The reaction 45 mixture is warmed to room temperature and then carefully added to water. After washing with n-hexane, the aqueous phase is acidified with 1 NHC1. A colourless solid precipi tates out and is, after filtration with Suction and air-drying, used without further purification for the next step. 50 0.5 g (1.45 mmol) of (2E)-3-chloro-2-3,5-dichloro-4- Step 3: (2E)-3-Chloro-2-3,5-dichloro-4-(dimethy (dimethylamino)phenyl-4,4,4-trifluorobut-2-enenitrile, lamino)phenyl-4,4,4-trifluorobut-2-enenitrile) 0.224 g (1.45 mmol) of 2-ethoxy-3-hydrazinopyrazine and 55 0.376 g (2.91 mmol) of N-ethyldiisopropylamine in 25 ml of THF are stirred under reflux for 6 hours. After cooling, the F solvent is distilled offunder reduced pressure, 30 ml of water F are added to the residue and the mixture is extracted repeat O edly with dichloromethane. The separated organic phases are F 60 combined, dried over magnesium Sulphate, filtered and con C centrated. The residue is stirred with n-pentane and the pre S Cl C cipitate formed is filtered off with suction and air-dried. This N 'N1 gives 0.548 g (75.9% of theory) of the title compound as a N o? N C colourless solid. 65 1H NMR (400 MHz, DMSO-d6), 8 8.44 (d. 1H), 8.25 (d. C 1H), 7.33 (s. 2H), 5.97 (bs, 2H, NH), 4.47 (q, 2H), 2.86 (s, 6H), 1.32 (t, 3H). US 9,066,945 B2 23 24 USE EXAMPLES effects on the mortality of cat fleas (Ctenocephalides felis) at 0.06-1.4 g/dm of component A-1 after 48 h. According to S. R. Colby, Weeds 15 (1967), 20-22, the For Example B-18 from Table 3, mixtures with component expected action for a given combination of two active com A-1 of A-1:B-18 of from 1:25 to 25:1 showed synergistic pounds can be calculated as follows: if effects on the mortality of brown dog ticks (Rhipicephalus X is the kill rate, expressed in % of the untreated control, sanguineus) at 0.06-1.4 Lig/dm of component A-1 after 48 h. when employing active compound A at an application rate For Example B-20 from Table 3, mixtures with component of mg/ha or in a concentration of m ppm, A-1 of A-1:B-20 of from 1:25 to 5:1 showed synergistic Y is the kill rate, expressed in % of the untreated control, effects on the mortality of cat fleas (Ctenocephalides felis) at when employing active compound Batan application rate 10 0.06-1.4 g/dm of component A-1 after 24 h. Against brown dog ticks (Rhipicephalus sanguineus), mix of ng/ha or in a concentration of n ppm and tures of A-1:B-20 in a ratio of 5:1 and higher (in the present E is the kill rate, expressed in '% of the untreated control, when application "higher means that the ratio seen as a fraction has employing active compounds A and B at application rates a greater value, i.e. a ratio of 6:1 is higher than 5:1 and 6:2 is of m and ng/ha or in a concentration of m and n ppm, 15 lower than 5:1) had a synergistic effect on the mortality at 1.4 then ug/dm of component A-1 after 48 h. For Example B-25 from Table 3, mixtures with component A-1 of A-1:B-25 of from 1: 125 to 25:1 showed synergistic effects on the mortality of cat fleas (Ctenocephalides felis) at 7.2 g/dm of component A-1 after 48 h. Against brown dog ticks (Rhipicephalus sanguineus), mix If the actual kill rate exceeds the calculated value, the tures of A-1:B-25 in a ratio of 25:1 and higher were synergis killing action of the combination is Superadditive, i.e. a syn tically active at 7.2 g/dm of component A-1 after 24 h. ergistic effect is present. In this case, the actually observed For Example B-27 from Table 3, mixtures with component kill rate must exceed the value calculated using the above 25 A-1 of A-1:B-27 of from 1: 125 to 25:1 showed synergistic formula for the expected kill rate (E). effects on the mortality of cat fleas (Ctenocephalides felis) at In vitro contact tests with ticks and fleas 0.06-7.2 ug/dm of component A-1 after 24 h. From Table 1, representatives of important classes of active Against brown dog ticks (Rhipicephalus sanguineus), mix compounds (component B) were now tested in combination tures of A-1:B-27 in a ratio of from 125:1 to 1:125 were 30 synergistically active at 1.4Lig/dm of component A-1 after 48 with pyrazine derivatives of the formula (I) according to the h. invention as component A against arachnids and insects. To For Example B-29 from Table 3, mixtures with component this end, roll-necked test tubes were coated with a solution of A-1 of A-1:B-29 of from 1:5 to 25:1 showed synergistic active compound A or B or a combination of the two in effects on the mortality of cat fleas (Ctenocephalides felis) at acetone (2h of Swing rotation at 30 rpm in a fume cupboard). 35 7.2 g/dm of component A-1 after 48 h. After evaporation of the solvent, the test tubes were populated Against brown dog ticks (Rhipicephalus sanguineus), mix with 10-20 adult fleas (Ctenocephalides felis) or with 5-10 tures of A-1:B-29 in a ratio of from 1:5 to 5:1 were synergis ticks (adult Rhipicephalus sanguineus) and closed with a tically active at 1.4 g/dm of component A-1 after 48 h. perforated plastic lid. After 24 h and after 48 h, the activity For Example B-37 from Table 3, mixtures with component was determined and the potential synergistic effect of the 40 A-1 of A-1:B-37 of from 1:125 to 5:1 showed synergistic active compound combination was evaluated using the for effects on the mortality of brown dog ticks (Rhipicephalus mula described above. sanguineus) at 1.4 Lig/dm of component A-1 after 48 h. Against cat fleas (Ctenocephalides felis), mixtures of A-1: For Example A1 B-37 in a ratio of 1:5 were synergistically active at 1.4g/dm 45 of component A-1 after 48 h. For Example B-1 from Table 3, mixtures of A-1:B-1 of from 1:5 to 1:25 showed synergistic effects on the mortality of For Example A14 cat fleas (Ctenocephalides felis) at 7.2 Lig/dm of component B-1 after 48 h. For Example B-1 from Table 3, mixtures of A-14:B-1 of Against brown dog ticks (Rhipicephalus sanguineus), mix 50 from 1:1 to 1:125 showed synergistic effects on the mortality tures of A-1:B-1 in a ratio of from 1:1 to 1:25 were synergis of cat fleas (Ctenocephalides felis) at 7.2 Lig/dm of compo tically active at 1.4 ug/dm of component B-1 after 24 and 48 nent B-1 after 48 h. h. Against brown dog ticks (Rhipicephalus sanguineus), mix For Example B-11 from Table 3, as expected, no insecti tures of A-14:B-1 in a ratio of from 1:1 to 1:25 were syner cidal activity was observed in the contact test method, since 55 gistically active at 7.2 and 1.4Lig/dm of component B-1 after the active compound class of these amidines shows virtually 24 h. no relevant insecticidal activity in Veterinary indications. For Example B-11 from Table 3, as expected, no insecti Accordingly, under the test conditions, the insecticidal activ cidal activity was observed in the contact test method, since ity of component A-1 in combinations with B-11 was the active compound class of these amidines shows virtually unchanged. 60 no relevant insecticidal activity in Veterinary indications. In the case of mixtures with component A-1, mixtures of Accordingly, under the test conditions, the insecticidal activ A-1:B-11 of from 125:1 to 1:25 showed strong synergistic ity of component A-14 in combinations with B-11 was virtu effects on the mortality of brown dog ticks (Rhipicephalus ally unchanged. sanguineus) at 0.288-7.2 ug/dm of component A-1 after 24h In the case of mixtures with component B-11, mixtures of and 48 h. 65 A-14:B-11 of from 25:1 to 1:125 showed synergistic effects For Example B-18 from Table 3, mixtures with component on the mortality of brown dog ticks (Rhipicephalus San A-1 of A-1:B-18 of from 1:25 to 25:1 showed synergistic guineus) at 0.288-7.2 g/dm of component A-14 after 48 h. US 9,066,945 B2 25 26 For Example B-18 from Table 3, mixtures with component For Example B-18 from Table 3, mixtures with component A-14 of A-14: B-18 of from 1:25 to 25:1 showed synergistic A-15 showed no changes in activity against brown dog ticks effects on the mortality of cat fleas (Ctenocephalides felis) at under the test conditions. 0.06-1.4 ug/dm of component A-14 after 48 h. For Example B-20 from Table 3, mixtures with component For Example B-18 from Table 3, mixtures with component A-15 of A-15: B-20 of 1:25 and higher showed synergistic A-14 of A-1:B-18 of from 1:25 to 5:1 showed synergistic effects on the mortality of cat fleas (Ctenocephalides felis) at effects in the activity against brown dog ticks (Rhipicephalus 0.06-7.2 g/dm of component A-15 after 24 h. sanguineus) at 1.4 Lig/dm of component B-18 after 48 h. Against brown dog ticks (Rhipicephalus sanguineus), mix For Example B-20 from Table 3, mixtures with component tures of A-15: B-20 in a ratio of 5:1 and higher acted syner 10 gistically on the mortality at 7.2-36 ug/dm of component A-14 of A-14:B-20 of from 1: 125 to 5:1 showed synergistic A-15 after 48 h. effects on the mortality of cat fleas (Ctenocephalides felis) at For Example B-25 from Table 3, mixtures with component 0.28-7.2 ug/dm of component A-14 after 24 h and 48 h. A-15 of A-15: B-25 of from 1:125 to 25:1 showed synergistic Against brown dog ticks (Rhipicephalus sanguineus), mix effects on the mortality of cat fleas (Ctenocephalides felis) at tures of A-14:B-20 in a ratio of 5:1 and higher had synergistic 15 0.28-7.2 ug/dm of component A-15 after 48 h. effects on the mortality at 1.4-7.2 g/dm of component A-14 Against brown dog ticks (Rhipicephalus sanguineus), mix after 24 h and 48 h. tures of A-15: B-25 in a ratio of from 1:125 to 5:1 were For Example B-25 from Table 3, mixtures with component synergistically active at 1.44-180g/dm of component A-15 A-14 of A-14: B-25 of from 1: 125 to 5:1 showed synergistic after 24 and 48 h. effects in the activity against cat fleas (Ctenocephalides felis) For Example B-27 from Table 3, mixtures with component at 7.2-36 ug/dm of component A-14 after 48 h. A-15 of A-15: B-27 of from 1:25 to 25:1 showed synergistic Against brown dog ticks (Rhipicephalus sanguineus), mix effects on the mortality of cat fleas (Ctenocephalides felis) at tures of B-25: A-14 in a ratio of 5:1 and higher were syner 1.44-7.2 ug/dm of component A-15 after 48 h. gistically active at 0.28-1.4 Lig/dm of component A-14 after Against brown dog ticks (Rhipicephalus sanguineus), mix 24 h. 25 tures of A-15: B-27 in a ratio of 25:1 to 1:125 showed syner For Example B-27 from Table 3, mixtures with component gistic effects on the mortality at 0.06-7.2 ug/dm of compo A-14 of A-14:B-27 of from 1:125 to 25:1 showed synergistic nent A-1 after 48 h. effects on the mortality of cat fleas (Ctenocephalides felis) at For Example B-29 from Table 3, mixtures with component 7.2-36 ug/dm of component A-14 after 24 h. A-15 of A-15: B-29 of from 1:5 to 1:125 showed synergistic 30 effects on the mortality of cat fleas (Ctenocephalides felis) at Against brown dog ticks (Rhipicephalus sanguineus), mix 7.2 g/dm of component A-15 after 24 h. tures of A-14:B-27 in a ratio of from 5:1 to 1:125 were Against brown dog ticks (Rhipicephalus sanguineus), mix synergistically active at 1.4-36 ug/dm of component A-14 tures of A-15: B-29 in a ratio of 1:5 to 25:1 showed synergistic after 48 h. effects on the mortality at 0.28-1.4 g/dm of component For Example B-29 from Table 3, mixtures with component 35 A-15 after 24 h. A-14 of A-14: B-29 of from 1:5 to 125:1 showed synergistic For Example B-37 from Table 3, mixtures with component effects in the activity against cat fleas (Ctenocephalides felis) A-15 of A-15: B-37 of from 1:125 to 125:1 showed synergistic at 1.44-7.2 ug/dm of component A-14 after 24 h. effects on the mortality of brown dog ticks (Rhipicephalus Against brown dog ticks (Rhipicephalus sanguineus), mix sanguineus) at 7.2-180 g/dm of component A-15 after 48 h. tures of A-14: B-29 in a ratio of from 1:125 to 125:1 were 40 The invention claimed is: synergistically active at 0.06-1.4 Lig/dm of component A-14 1. A veterinary pharmaceutical combination comprising, after 48 h. as component A, a compound of the general formula (I) For Example A15 45 (I) For Example B-1 from Table 3, mixtures of A-15: B-1 of from 5:1 to 1:125 showed synergistic effects on the mortality of cat fleas (Ctenocephalides felis) at 1.4 Lig/dm of compo nent B-1 after 48 h. Against brown dog ticks (Rhipicephalus sanguineus), mix 50 tures of A-15: B-1 in a ratio of 1:5 were synergistically active at 0.288 g/dm of component B-1 after 24 and 48 h. For Example B-11 from Table 3, as expected, no insecti cidal activity was observed in the contact test method, since in which the active compound class of these amidines shows virtually 55 X represents phenyl, 2-pyridyl or 3-pyridyl, each of which no relevant insecticidal activity in Veterinary indications. is substituted by one or more substituents selected from Accordingly, under the test conditions, the insecticidal activ the group consisting of halogen, alkyl, haloalkyl, alkoxy, ity of component A-15 in combinations with B-11 was alkoxyalkyl, alkoxyalkoxy, cycloalkyl, alkenyloxy, unchanged. alkynyloxy, benzyloxy, cycloalkylalkoxy, haloalkoxy, In the case of mixtures with component A-15, mixtures of 60 haloalkoxyalkyl, alkylsulphanyl, haloalkylsulphanyl, A-15:B-11 of from 125:1 to 1:25 showed synergistic effects alkylsulphinyl, haloalkylsulphinyl, alkylsulphonyl, on the mortality of brown dog ticks (Rhipicephalus San haloalkylsulphonyl, cyano, nitro, alkylcarbonyl, guineus) at 0.288-7.2 g/dm of component A-1 after 48 h. alkoxycarbonyl, alkoxycarbonylalkyl, carboxyl, car For Example B-18 from Table 3, mixtures with component boxamide, dialkylcarboxamide, trialkylsilyl, amino, A-15 of A-15: B-18 of from 1:25 to 25:1 showed synergistic 65 alkylamino, dialkyl-amino, alkylsulphonylamino, effects on the mortality of cat fleas (Ctenocephalides felis) at dialkylsulphonylamino, formyl, —CH=NO H. 0.28-7.2 ug/dm of component A-15 after 24 h. -CH=NO-alkyl, -CH=NO-halolkyl, -C(CH)— US 9,066,945 B2 27 28 NO H. C(CH)—NO-alkyl, -C(CH)—NO-ha - C(CH)—NO-alkyl, —C(CH)—NO-haloalkyl, loalkyl; and phenyl, 2-pyridyl and 3-pyridyl which are nitro, hydroxyl, SH, alkoxy, alkylsulphanyl, haloalkyl optionally Substituted by one or more halogen atoms, Sulphanyl, alkylsulphinyl, haloalkylsulphinyl, alkylsul cyano, nitro, alkyl, alkoxy or haloalkyl, where vicinal phonyl or haloalkylsulphonyl, alkyl, haloalkyl, alkoxy and/or haloalkoxy groups at the 5 R represents halogen, alkyl, haloalkyl, hydroxyl, alkoxy, phenyl substituent, 2-pyridyl substituent or 3-pyridyl alkoxyalkyl, alkoxyalkoxy, cycloalkyl, alkenyloxy, substituent together with the carbonatoms to which they alkynyloxy, benzyloxy, cycloalkylalkoxy, haloalkoxy, are attached may form a five- to six-membered cyclic haloalkoxyalkyl, -SH, alkyl-Sulphanyl, haloalkylsul system which contains 0 to oxygen or nitrogen atoms, phanyl, alkylsulphinyl, haloalkylsulphinyl, alkylsulpho where two oxygenatoms are not directly attached to one 10 nyl, haloalkylsulphonyl, cyano, nitro, alkylcarbonyl, another, and whose alkyl moiety may optionally be Sub alkoxycarbonyl, alkoxycarbonylalkyl, carboxyl, car stituted by one or more halogen atoms and/or further boxamide, dialkylcarboxamide, trialkylsilyl, amino, alkyl radicals, alkylamino, dialkylamino, alkylsulphonylamino, R" represents alkyl which is optionally monosubstituted or dialkylsulphonylamino, formyl, —CH=NO H. independently poly Substituted by alkoxy, haloalkoxy, 15 -CH=NO-alkyl, -CH=NO-haloalkyl, -C(CH)— alkylsulphanyl, haloalkylsulphanyl, alkylsulphinyl, NO H. C(CH)—NO-alkyl, -C(CH)—NO-ha haloalkylsulphinyl, alkylsulphonyl, haloalkylsulpho loalkyl, heteroaryl, where the heteroaromatic ring may nyl, alkylcarbonyl, alkoxycarbonyl, hydroxyl and/or optionally be mono- or polysubstituted by one or more cycloalkyl; alkenyl which is optionally monosubstituted substituents independently of one another selected from or independently poly Substituted by halogen, alkoxy, the group consisting of halogen, alkyl, haloalkyl and haloalkoxy, alkylsulphanyl, haloalkylsulphanyl, alkyl alkoxy, Sulphinyl, haloalkylsulphinyl, alkylsulphonyl, or N-oxides or salts thereof, haloalkylsulphonyl, alkylcarbonyl, alkoxycarbonyl and/ and, as component B, an active compound selected from the or cycloalkyl, cycloalkyl which is optionally monoSub group consisting of: (I-1) acetylcholinesterase (AChE) stituted or independently polysubstituted by alkyl, 25 inhibitors; (I-2) GABA-gated chloride channel antagonists; haloalkyl and/or halogen; haloalkyl which is optionally (I-3) sodium channel modulators/voltage-dependent sodium monosubstituted or independently polysubstituted by channel blockers; (I-4) nicotinergic acetylcholine receptor alkoxy, alkylsulphanyl, haloalkylsulphanyl, alkylsul agonists; (I-5) allosteric acetylcholine receptor modulators phinyl, haloalkylsulphinyl, alkylsulphonyl, haloalkyl (agonists); (I-6) chloride channel activators; (I-7) juvenile Sulphonyl and/or phenyl which is optionally monoSub 30 hormone analogues; (I-8) mite growth inhibitors; (I-9) Slo-1 stituted or independently polysubstituted by halogen, and latrophilin receptor agonists; (I-10) oxidative phospho alkyl, haloalkyl and/or alkoxy; phenyl which is option rylation inhibitors, ATP disruptors; (I-12) nicotinergic acetyl ally monosubstituted or independently polysubstituted choline receptor antagonists; (I-13) chitin biosynthesis by halogen, alkyl, haloalkyl and/or alkoxy; benzyl inhibitors, type 0; (I-14) chitinbiosynthesis inhibitors, type 1: which is optionally monosubstituted or independently 35 (I-15) moulting disruptors; (I-16) ecdysone agonists/disrup poly Substituted by halogen, alkyl, haloalkyl and/or tors; (I-17) octopaminergic agonists; (I-18) complex-III elec alkoxy; cyano, formyl, alkylcarbonyl, —CH=NO H. tron transport inhibitors; (I-19) complex-I electron transport -CH=NO-alkyl, -CH=NO-haloalkyl, -C(CH)— inhibitors; (I-20) voltage-dependent sodium channel block NO H. C(CH)—NO-alkyl or - C(CH)—NO-ha ers; (I-21) inhibitors of acetyl-CoA carboxylase; (I-22) com loalkyl, 40 plex-II electron transport inhibitors; (I-23) ryanodine recep R represents optionally substituted amino, where amino tor effectors; (I-24) active compounds selected from may be monosubstituted or independently disubstituted benzoximate, chinomethionat, cyflumetofen, pyridalyl, Sul by alkyl, haloalkyl, alkoxyalkyl, alkylsulphanylalkyl, foxaflor, and penigequinolone A, and (I-25) Synergists alkylsulphinylalkyl, alkylsulphonylalkyl, alkylcarbo MGK264 and piperonylbutoxide (PBO). nyl, cycloalkyl, cycloalkylalkyl, alkenyl, where the radi 45 2. The combination according to claim 1, comprising, as cals listed above are optionally Substituted by halogen, component B, an active compound selected from the group cyano, alkoxy, alkoxycarbonyl and phenyl, where the consisting of: (I-2) GABA-gated chloride channel antago phenyl ring is optionally mono- or poly Substituted by nists; (I-3) sodium channel modulators/voltage-dependent one or more Substituents independently of one another Sodium channel blockers; (I-4) nicotinergic acetylcholine Selected from the group consisting of halogen, alkyl, 50 receptor agonists; (I-5) allosteric acetylcholine receptor haloalkyl and alkoxy; alkynyl, alkoxycarbonyl, alkeny modulators (agonists); (I-6) chloride channel activators; loxycarbonyl, alkinyloxycarbonyl, alkoxycarbonyla (I-17) octopaminergic agonists; and (I-25) Synergists lkyl, alkoxycarbonylcarbonyl, heterocyclyl, heteroaryl, MGK264 and piperonylbutoxide (PBO). heterocyclylalkyl or heteroarylalkyl, where the hetero 3. The combination according to claim 1, comprising, as cyclic or heteroaromatic ring may optionally be mono 55 component A, a compound selected from the group consisting or poly Substituted by one or more Substituents indepen of: dently of one another selected from the group consisting of halogen, alkyl, haloalkyl and alkoxy; benzyl or phe A-1 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-ethoxypyrazin-2-yl)-3- nylcarbonyl, where the phenyl ring in benzyl and phe (trifluoromethyl)-1H-pyrazole-5-amine nylcarbonyl is optionally mono- or polysubstituted by 60 A-2 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2-yl)-3- one or more Substituents independently of one another (trifluoromethyl)-1H-pyrazole-5-amine Selected from the group consisting of halogen, alkyl, A-3 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2-yl)- haloalkyl and alkoxy, and 3-methyl-1H-pyrazole-5-amine A-4 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-ethoxypyrazin-2-yl)- R, R independently of one another represent hydrogen, 3-ethyl-1H-pyrazole-5-amine halogen, alkyl, cycloalkyl, haloalkyl, cyano, hydroxyl, 65 A-5 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2-yl)- formyl, alkylcarbonyl, -CH=NO-H, -CH=NO 3-ethyl-1H-pyrazole-5-amine alkyl, -CH=NO-halo-alkyl, -C(CH)—NO H. US 9,066,945 B2 29 30 -continued Oxime, moxidectin, Selamectin; amitraz, cymiazole, demidi traz: piperonyl butoxide, and MGK264. A-6 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2-yl)- 3-isopropyl-1H-pyrazole-5-amine 11. The combination according to claim 1, wherein A is A-7 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2-yl)- 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2- 3-cyclopropyl-1H-pyrazole-5-amine yl)-3-methyl-1H-pyrazole-5-amine, and B is selected from A-8 4-(7-bromo-1,3-benzodioxol-5-yl)-1-(3-ethoxypyrazin-2-yl)- the group consisting of endosulphan (alpha-), lindane; 3-(trifluoromethyl)-1H-pyrazole-5-amine fipronil, pyriprole; A1443; allethrin, bioallethrin, permethrin, A-9 4-(7-bromo-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2-yl)- 3-(trifluoromethyl)-1H-pyrazole-5-amine phenothrin, resmethrin, tetramethrin: cyfluthrin (beta-), A-10 4-(7-bromo-1,3-benzodioxol-5-yl)-1-(3-ethoxypyrazin-2-yl)- cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-), delta 3-ethyl-1H-pyrazole-5-amine 10 methrin, fenvalerate, flucythrinate, flumethrin, fluvalinate A-11 4-(7-bromo-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2-yl)- 3-ethyl-1H-pyrazole-5-amine (tau-): etofemproX, Silafluofen; chlothianidin, dinotefuran, A-12 1-(3-ethoxypyrazin-2-yl)-3-(triluoromethyl)-4-7- imidacloprid, nitenpyram, thiacloprid; spinosad, spinetoram; (trifluoromethyl)-1,3-benzodioxol-5-yl)-1H-pyrazole-5-amine doramectin, eprinomectin, ivermectin, milbemycin oxime, A-13 1-(3-methoxypyrazin-2-yl)-3-(triluoromethyl)-4-7- moxidectin, Selamectin; amitraz, cymiazole, demiditraz: pip (trifluoromethyl)-1,3-benzodioxol-5-yl)-1H-pyrazole-5-amine 15 eronyl butoxide, and MGK264. A-14 4-(3,5-dichloro-4-methoxyphenyl)-1-(3-ethoxypyrazin-2-yl)-3- (trifluoromethyl)-1H-pyrazole-5-amine; and 12. The combination according to claim 1, wherein A is A-15 4-3,5-dichloro-4-(dimethylamino)phenyl-1-(3-ethoxypyrazin 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-ethoxypyrazin-2- 2-yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine. yl)-3-ethyl-1H-pyrazole-5-amine, and B is selected from the group consisting of endosulphan (alpha-), lindane; fipronil. pyriprole; A1443; allethrin, bioallethrin, permethrin, pheno 4. The combination according to claim 1, comprising, as thrin, resmethrin, tetramethrin: cyfluthrin (beta-), cyhalothrin component B, a compound selected from the group consisting (lambda-), cypermethrin (alpha-, Zeta-), deltamethrin, fenval of endosulphan (alpha-), lindane; fipronil, pyriprole; A1443; erate, flucythrinate, flumethrin, fluvalinate (tau-): etofenprox. allethrin, bioallethrin, permethrin, phenothrin, resmethrin, Silafluofen; chlothianidin, dinotefuran, imidacloprid, niten tetramethrin: cyfluthrin (beta-), cyhalothrin (lambda-), cyper 25 pyram, thiacloprid; spinosad, spinetoram; doramectin, epri methrin (alpha-, Zeta-), deltamethrin, fenvalerate, flucythri nomectin, ivermectin, milbemycin oxime, moxidectin, sel nate, flumethrin, fluvalinate (tau-): etofemprox, silafluofen; amectin; amitraz, cymiazole, demiditraz: piperonylbutoxide, chlothianidin, dinotefuran, imidacloprid, nitenpyram, thia and MGK264. cloprid; spinosad, spinetoram; doramectin, eprinomectin, 13. The combination according to claim 1, wherein A is ivermectin, milbemycin Oxime, moxidectin, Selamectin; ami 30 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2- traZ, cymiazole, demiditraz: piperonyl butoxide, and yl)-3-ethyl-1H-pyrazole-5-amine, and B is selected from the MGK264. group consisting of endosulphan (alpha-), lindane; fipronil, 5. The combination according to claim 1, wherein A is pyriprole; A1443; allethrin, bioallethrin, permethrin, pheno 4-(3,5-Dichloro-4-methoxyphenyl)-1-(3-ethoxypyrazin-2- thrin, resmethrin, tetramethrin: cyfluthrin (beta-), cyhalothrin yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine. 35 (lambda-), cypermethrin (alpha-, Zeta-), deltamethrin, fenval 6. The combination according to claim 1, wherein A is erate, flucythrinate, flumethrin, fluvalinate (tau-): etofenprox. 4-3,5-Dichloro-4-(dimethylamino)phenyl-1-(3-ethoxy Silafluofen; chlothianidin, dinotefuran, imidacloprid, niten pyrazin-2-yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine. pyram, thiacloprid; spinosad, spinetoram; doramectin, epri 7. A method for controlling ectoparasites comprising nomectin, ivermectin, milbemycin oxime, moxidectin, sel administering to an animal in need thereof an effective 40 amectin; amitraz, cymiazole, demiditraz: piperonylbutoxide, amount of a combination according to claim 1. and MGK264. 8. The method according to claim 7, wherein components 14. The combination according to claim 1, wherein A is A and B of the combination are administered simultaneously. 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2- 9. The combination according to claim 1, wherein A is yl)-3-isopropyl-1H-pyrazole-5-amine, and B is selected from 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-ethoxypyrazin-2- 45 the group consisting of endosulphan (alpha-), lindane; yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine, and B is fipronil, pyriprole; A1443; allethrin, bioallethrin, permethrin, selected from the group consisting of endosulphan (alpha-), phenothrin, resmethrin, tetramethrin: cyfluthrin (beta-), lindane; fipronil, pyriprole; A1443; allethrin, bioallethrin, cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-), delta permethrin, phenothrin, resmethrin, tetramethrin: cyfluthrin methrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (beta-), cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-). 50 (tau-): etofemproX, Silafluofen; chlothianidin, dinotefuran, deltamethrin, fenvalerate, flucythrinate, flumethrin, fluvali imidacloprid, nitenpyram, thiacloprid; spinosad, spinetoram; nate (tau-): etofenproX, Silafluofen; chlothianidin, dinotefu doramectin, eprinomectin, ivermectin, milbemycin oxime, ran, imidacloprid, nitenpyram, thiacloprid; spinosad, spin moxidectin, Selamectin; amitraz, cymiazole, demiditraz: pip etoram; doramectin, eprinomectin, ivermectin, milbemycin eronyl butoxide, and MGK264. oXime, moxidectin, Selamectin; amitraz, cymiazole, demidi 55 15. The combination according to claim 1, wherein A is traz: piperonyl butoxide, and MGK264. 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2- 10. The combination according to claim 1, wherein A is yl)-3-cyclopropyl-1H-pyrazole-5-amine, and B is selected 4-(7-chloro-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2- from the group consisting of endosulphan (alpha-), lindane; yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine, and B is fipronil, pyriprole; A1443; allethrin, bioallethrin, permethrin, selected from the group consisting of endosulphan (alpha-), 60 phenothrin, resmethrin, tetramethrin: cyfluthrin (beta-), lindane; fipronil, pyriprole; A1443; allethrin, bioallethrin, cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-), delta permethrin, phenothrin, resmethrin, tetramethrin: cyfluthrin methrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (beta-), cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-). (tau-): etofemproX, Silafluofen; chlothianidin, dinotefuran, deltamethrin, fenvalerate, flucythrinate, flumethrin, fluvali imidacloprid, nitenpyram, thiacloprid; spinosad, spinetoram; nate (tau-): etofenproX, Silafluofen; chlothianidin, dinotefu 65 doramectin, eprinomectin, ivermectin, milbemycin oxime, ran, imidacloprid, nitenpyram, thiacloprid; spinosad, spin moxidectin, Selamectin; amitraz, cymiazole, demiditraz: pip etoram; doramectin, eprinomectin, ivermectin, milbemycin eronyl butoxide, and MGK264. US 9,066,945 B2 31 32 16. The combination according to claim 1, wherein A is romethyl)-1,3-benzodioxol-5-yl)-1H-pyrazole-5-amine, and 4-(7-bromo-1,3-benzodioxol-5-yl)-1-(3-ethoxypyrazin-2- B is selected from the group consisting of endosulphan (al yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine, and B is pha-), lindane; fipronil, pyriprole; A1443; allethrin, bioal Selected from the group consisting of endosulphan (alpha-). lethrin, permethrin, phenothrin, resmethrin, tetramethrin; lindane; fipronil, pyriprole: A1443; allethrin, bioallethrin, cyfluthrin (beta-), cyhalothrin (lambda-), cypermethrin (al permethrin, phenothrin, resmethrin, tetramethrin: cyfluthrin pha-, Zeta-), deltamethrin, fenvalerate, flucythrinate, flu (beta-), cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-). methrin, fluvalinate (tau-): etofenprox, silafluofen; chlo deltamethrin, fenvalerate, flucythrinate, flumethrin, fluvali thianidin, dinotefuran, imidacloprid, nitenpyram, nate (tau-): etofenprox, silafluofen; chlothianidin, dinotefu thiacloprid; spinosad, spinetoram; doramectin, eprinomectin, ran, imidacloprid, nitenpyram, thiacloprid; spinosad, spin 10 ivermectin, milbemycin Oxime, moxidectin, selamectin; ami etoram; doramectin, eprinomectin, ivermectin, milbemycin traZ, cymiazole, demiditraz: piperonyl butoxide, and Oxime, moxidectin, Selamectin; amitraz, cymiazole, demidi MGK264. traz: piperonyl butoxide, and MGK264. 21. The combination according to claim 1, wherein A is 17. The combination according to claim 1, wherein A is 1-(3-methoxypyrazin-2-yl)-3-(triluoromethyl)-4-7-(trifluo 4-(7-bromo-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2- 15 romethyl)-1,3-benzodioxol-5-yl)-1H-pyrazole-5-amine, and yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine, and B is B is selected from the group consisting of endosulphan (al Selected from the group consisting of endosulphan (alpha-). pha-), lindane; fipronil, pyriprole: A1443; allethrin, bioal lindane; fipronil, pyriprole; A1443; allethrin, bioallethrin, lethrin, permethrin, phenothrin, resmethrin, tetramethrin; permethrin, phenothrin, resmethrin, tetramethrin: cyfluthrin cyfluthrin (beta-), cyhalothrin (lambda-), cypermethrin (al (beta-), cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-), pha-, Zeta-), deltamethrin, fenvalerate, flucythrinate, flu deltamethrin, fenvalerate, flucythrinate, flumethrin, fluvali methrin, fluvalinate (tau-): etofemprox, silafluofen; chlo nate (tau-): etofenprox, silafluofen; chlothianidin, dinotefu thianidin, dinotefuran, imidacloprid, nitenpyram, ran, imidacloprid, nitenpyram, thiacloprid; spinosad, spin thiacloprid; spinosad, spinetoram; doramectin, eprinomectin, etoram; doramectin, eprinomectin, ivermectin, milbemycin ivermectin, milbemycin oxime, moxidectin, selamectin; ami Oxime, moxidectin, Selamectin; amitraz, cymiazole, demidi 25 traZ, cymiazole, demiditraz: piperonyl butoxide, and traz: piperonyl butoxide, and MGK264. MGK264. 18. The combination according to claim 1, wherein A is 22. The combination according to claim 1, wherein A is 4-(7-bromo-1,3-benzodioxol-5-yl)-1-(3-ethoxypyrazin-2- 4-(3,5-dichloro-4-methoxyphenyl)-1-(3-ethoxypyrazin-2- yl)-3-ethyl-1H-pyrazole-5-amine, and B is selected from the yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine; and, and B is group consisting of endosulphan (alpha-), lindane; fipronil, 30 Selected from the group consisting of endosulphan (alpha-). pyriprole; A1443; allethrin, bioallethrin, permethrin, pheno lindane; fipronil, pyriprole; A1443; allethrin, bioallethrin, thrin, resmethrin, tetramethrin: cyfluthrin (beta-), cyhalothrin permethrin, phenothrin, resmethrin, tetramethrin: cyfluthrin (lambda-), cypermethrin (alpha-, Zeta-), deltamethrin, fenval (beta-), cyhalothrin (lambda-), cypermethrin (alpha-, Zeta-), erate, flucythrinate, flumethrin, fluvalinate (tau-): etofemprox. deltamethrin, fenvalerate, flucythrinate, flumethrin, fluvali silafluofen; chlothianidin, dinotefuran, imidacloprid, niten 35 nate (tau-): etofemprox. Silafluofen; chlothianidin, dinotefu pyram, thiacloprid; spinosad, spinetoram; doramectin, epri ran, imidacloprid, nitenpyram, thiacloprid; spinosad, spin nomectin, ivermectin, milbemycin oxime, moxidectin, sel etoram; doramectin, eprinomectin, ivermectin, milbemycin amectin; amitraz, cymiazole, demiditraz: piperonylbutoxide, Oxime, moxidectin, Selamectin; amitraz, cymiazole, demidi and MGK264. traz: piperonyl butoxide, and MGK264. 19. The combination according to claim 1, wherein A is 40 23. The combination according to claim 1, wherein A is 4-(7-bromo-1,3-benzodioxol-5-yl)-1-(3-methoxypyrazin-2- 4-3,5-dichloro-4-(dimethylamino)phenyl)-1-(3-ethoxy yl)-3-ethyl-1H-pyrazole-5-amine, and B is selected from the pyrazin-2-yl)-3-(trifluoromethyl)-1H-pyrazole-5-amine, and group consisting of endosulphan (alpha-), lindane; fipronil, B is selected from the group consisting of endosulphan (al pyriprole; A1443; allethrin, bioallethrin, permethrin, pheno pha-), lindane; fipronil, pyriprole; A1443; allethrin, bioal thrin, resmethrin, tetramethrin: cyfluthrin (beta-), cyhalothrin 45 lethrin, permethrin, phenothrin, resmethrin, tetramethrin; (lambda-), cypermethrin (alpha-, Zeta-), deltamethrin, fenval cy fluthrin (beta-), cyhalothrin (lambda-), cypermethrin (al erate, flucythrinate, flumethrin, fluvalinate (tau-): etofemprox. pha-, Zeta-), deltamethrin, fenvalerate, flucythrinate, flu silafluofen; chlothianidin, dinotefuran, imidacloprid, niten methrin, fluvalinate (tau-): etofenprox, silafluofen; chlo pyram, thiacloprid; spinosad, spinetoram; doramectin, epri thianidin, dinotefuran, imidacloprid, nitenpyram, nomectin, ivermectin, milbemycin oxime, moxidectin, sel 50 thiacloprid; spinosad, spinetoram; doramectin, eprinomectin, amectin; amitraz, cymiazole, demiditraz: piperonylbutoxide, ivermectin, milbemycin oxime, moxidectin, selamectin; ami and MGK264. traZ, cymiazole, demiditraz: piperonyl butoxide, and 20. The combination according to claim 1, wherein A is MGK264. 1-(3-ethoxypyrazin-2-yl)-3-(triluoromethyl)-4-7-(trifluo